# Tutorial #5: Qualitative genome-scale modeling using public data, Flux Balance Analysis (FBA)

Tutorial #5: Qualitative genome-scale modeling using public data, Flux Balance Analysis (FBA)

 
Author: Marc Weber  
Date: March 2016  
Affiliation: Center for Genomic Regulation (CRG), Barcelona, Spain.  
Notes: This tutorial was created for the course "Whole-cell modeling", taking place at CRG, Barcelona, April 3-8, 2016.

Author: Marc Weber
Date: March 2016
Affiliation: Center for Genomic Regulation (CRG), Barcelona, Spain.
Notes: This tutorial was created for the course "Whole-cell modeling", taking place at CRG, Barcelona, April 3-8, 2016.

 
## Exercise 1: Flux Balance Analysis (FBA)
In this exercise, we will learn to use the COBRA package to compute the optimal growth of E.coli under different conditions using flux balance analysis. We will use the full iJO1366 metabolic model of E.coli (Orth et al. 2011) that takes into accounts 1366 genes, 2251 metabolic reactions and 1136 unique metabolites. We will focus on the glucose central metabolism. The exercises are adapted from the tutorial "What is flux balance analysis?" by Orth, Thiele and Palsson (Orth et al. 2010).
### Outline
- Familiarizing with COBRA and Escher commands.
  - Get and download the iJO1366 from the BiGG database.
  - Loading iJO1366 model.
  - Drawing metabolic map.
  - Altering reaction bounds (adding and/or removing reactions).
  - Change the objective function (typically growth).
  - Solving for fluxes.
  - Draw metabolic map and fluxes using Escher in iPython.
  - Simulating optimal growth.
- Examples:
  - Compute and draw fluxes for aerobic/anaerobic growth on glucose.
  - Growth on alternate substrates
    - compute growth and fluxes on succinate: aerobic / anaerobic (no solution)
    - compute growth and fluxes on puryvate: aerobic / anaerobic (no solution)
  - Simulating different objective function, maximize ATP production.
  - Simulating single gene deletion, gene essentiality
  - Simulating double gene deletions, synthetic lethal
More information:
+ Orth, J. D., Thiele, I., & Palsson, B. Ø. (2010). What is flux balance analysis? Nature Biotechnology, 28(3), 245–248. http://doi.org/10.1038/nbt.1614
+ Maarleveld, T. R., Khandelwal, R. a., Olivier, B. G., Teusink, B., & Bruggeman, F. J. (2013). Basic concepts and principles of stoichiometric modeling of metabolic networks. Biotechnology Journal, 8, 997–1008. http://doi.org/10.1002/biot.201200291
+ Orth, J. D., Conrad, T. M., Na, J., Lerman, J. a, Nam, H., Feist, A. M., & Palsson, B. Ø. (2011). A comprehensive genome-scale reconstruction of Escherichia coli metabolism—2011. Molecular Systems Biology, 7(535), 1–9. http://doi.org/10.1038/msb.2011.65

Exercise 1: Flux Balance Analysis (FBA)

In this exercise, we will learn to use the COBRA package to compute the optimal growth of E.coli under different conditions using flux balance analysis. We will use the full iJO1366 metabolic model of E.coli (Orth et al. 2011) that takes into accounts 1366 genes, 2251 metabolic reactions and 1136 unique metabolites. We will focus on the glucose central metabolism. The exercises are adapted from the tutorial "What is flux balance analysis?" by Orth, Thiele and Palsson (Orth et al. 2010).

Outline

  • Familiarizing with COBRA and Escher commands.
    • Get and download the iJO1366 from the BiGG database.
    • Loading iJO1366 model.
    • Drawing metabolic map.
    • Altering reaction bounds (adding and/or removing reactions).
    • Change the objective function (typically growth).
    • Solving for fluxes.
    • Draw metabolic map and fluxes using Escher in iPython.
    • Simulating optimal growth.
  • Examples:
    • Compute and draw fluxes for aerobic/anaerobic growth on glucose.
    • Growth on alternate substrates
      • compute growth and fluxes on succinate: aerobic / anaerobic (no solution)
      • compute growth and fluxes on puryvate: aerobic / anaerobic (no solution)
    • Simulating different objective function, maximize ATP production.
    • Simulating single gene deletion, gene essentiality
    • Simulating double gene deletions, synthetic lethal

More information:

  • Orth, J. D., Thiele, I., & Palsson, B. Ø. (2010). What is flux balance analysis? Nature Biotechnology, 28(3), 245–248. http://doi.org/10.1038/nbt.1614
  • Maarleveld, T. R., Khandelwal, R. a., Olivier, B. G., Teusink, B., & Bruggeman, F. J. (2013). Basic concepts and principles of stoichiometric modeling of metabolic networks. Biotechnology Journal, 8, 997–1008. http://doi.org/10.1002/biot.201200291
  • Orth, J. D., Conrad, T. M., Na, J., Lerman, J. a, Nam, H., Feist, A. M., & Palsson, B. Ø. (2011). A comprehensive genome-scale reconstruction of Escherichia coli metabolism—2011. Molecular Systems Biology, 7(535), 1–9. http://doi.org/10.1038/msb.2011.65
 
### Import packages

Import packages

In [1]:
 
import escher
import escher.urls
import cobra
import cobra.test
import json
import os
import pandas
import re
from IPython.display import HTML
import seaborn
import matplotlib.pyplot as plt
%matplotlib inline
# If you want to increase the default width of the notebook
#HTML("<style>.container { width:100% !important; }</style>")
# The default height of the metabolic maps as displayed in the notebook
escherDefaultMapHeight = 800
In [2]:
 
d = escher.urls.root_directory
print('Escher directory: %s' % d)
Escher directory: /usr/local/lib/python3.5/dist-packages
 
#### Test COBRA package
All the tests should pass.

Test COBRA package

All the tests should pass.

In [ ]:
 
cobra.test.test_all()
 
### Draw metabolic maps with Escher

Draw metabolic maps with Escher

 
Escher is a web application for visualizing data on biological pathway maps.
More information:
- King, Z. A., Dräger, A., Ebrahim, A., Sonnenschein, N., Lewis, N. E., & Palsson, B. O. (2015). Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways. PLOS Computational Biology, 11(8), e1004321. http://doi.org/10.1371/journal.pcbi.1004321
- Documentation https://escher.readthedocs.org/en/latest/getting_started.html

Escher is a web application for visualizing data on biological pathway maps.

More information:

 
List available metabolic maps in the Escher package:

List available metabolic maps in the Escher package:

In [4]:
 
escher.list_available_maps()
Out[4]:
[{'map_name': 'e_coli_core.Core metabolism', 'organism': 'Escherichia coli'},
 {'map_name': 'iJO1366.Central metabolism', 'organism': 'Escherichia coli'},
 {'map_name': 'iJO1366.Fatty acid beta-oxidation',
  'organism': 'Escherichia coli'},
 {'map_name': 'iJO1366.Fatty acid biosynthesis (saturated)',
  'organism': 'Escherichia coli'},
 {'map_name': 'iJO1366.Nucleotide and histidine biosynthesis',
  'organism': 'Escherichia coli'},
 {'map_name': 'iJO1366.Nucleotide metabolism', 'organism': 'Escherichia coli'},
 {'map_name': 'RECON1.Amino acid metabolism (partial)',
  'organism': 'Homo sapiens'},
 {'map_name': 'RECON1.Carbohydrate metabolism', 'organism': 'Homo sapiens'},
 {'map_name': 'RECON1.Glycolysis TCA PPP', 'organism': 'Homo sapiens'},
 {'map_name': 'RECON1.Inositol retinol metabolism',
  'organism': 'Homo sapiens'},
 {'map_name': 'RECON1.Tryptophan metabolism', 'organism': 'Homo sapiens'},
 {'map_name': 'iMM904.Central carbon metabolism',
  'organism': 'Saccharomyces cerevisiae'}]
 
Draw the metabolic map of the textbook example of E. coli central carbon metabolism:

Draw the metabolic map of the textbook example of E. coli central carbon metabolism:

In [5]:
 
metabolicMap = escher.Builder(map_name='e_coli_core.Core metabolism')
metabolicMap.display_in_notebook(height=escherDefaultMapHeight)
Out[5]:
Phosphoglycerate kinasePGKPhosphogluconate dehydrogenaseGNDO2 transport diffusion O2tNAD P transhydrogenaseTHD222FumaraseFUMIsocitrate dehydrogenase (NADP)ICDHyrPyruvate dehydrogenasePDHPhosphoenolpyruvate carboxylasePPCEnolaseENOGlucose-6-phosphate isomerasePGIAmmonia reversible transportNH4tFructose-bisphosphataseFBPSuccinate exchangeEX_succ_eIsocitrate lyaseICLAdenylate kinaseADK12L-Glutamine exchangeEX_gln__L_eCO2 exchangeEX_co2_eTransaldolaseTALAPyruvate kinasePYKL glutamate transport via proton symport reversibleGLUt2rD-lactate exchangeEX_lac__D_ePyruvate exchangeEX_pyr_eRibulose 5-phosphate 3-epimeraseRPEH+ exchangeEX_h_eSuccinyl-CoA synthetase (ADP-forming)SUCOASPhosphofructokinasePFKL-Glutamate exchangeEX_glu__L_eTransketolaseTKT2Glutamine synthetaseGLNSNAD transhydrogenaseNADTRHD2-Oxogluterate dehydrogenaseAKGDHPyruvate formate lyasePFLO2 exchangeEX_o2_ePhosphoenolpyruvate carboxykinasePPCKPhosphate reversible transport via symportPIt2r2 oxoglutarate reversible transport via symportAKGt2rFructose-bisphosphate aldolaseFBATriose-phosphate isomeraseTPICytochrome oxidase bd (ubiquinol-8: 2 protons)CYTBD20.52Ribose-5-phosphate isomeraseRPIMalate synthaseMALSPhosphotransacetylasePTArGLNabcGLNabcMalic enzyme (NAD)ME1Glucose 6-phosphate dehydrogenaseG6PDH2rAcetate exchangeEX_ac_eGlutaminaseGLUNATP maintenance requirementATPMD-lactate dehydrogenaseLDH_DMalate dehydrogenaseMDHH2O transport via diffusionH2OtH2O exchangeEX_h2o_eTransketolaseTKT1CO2 transporter via diffusionCO2t2-Oxoglutarate exchangeEX_akg_ePhosphoenolpyruvate synthasePPS2D-Glucose exchangeEX_glc__D_eETOHt2rETOHt2rPhosphoglycerate mutasePGMEthanol exchangeEX_etoh_eAcetate kinaseACKrAmmonia exchangeEX_nh4_eGlutamate synthase (NADPH)GLUSy2Phosphate exchangeEX_pi_eFumarate transport via proton symport 2 H FUMt2_222Acetate reversible transport via proton symportACt2rD-glucose transport via PEP:Pyr PTSGLCptsSuccinate transport out via proton antiportSUCCt36-phosphogluconolactonasePGLGlyceraldehyde-3-phosphate dehydrogenaseGAPDFumarate exchangeEX_fum_eSuccinate transport via proton symport 2 H SUCCt2_222Glutamate dehydrogenase (NADP)GLUDyATP synthase (four protons for one ATP)ATPS4r43Citrate synthaseCSPyruvate transport in via proton symportPYRt2Malic enzyme (NADP)ME2Formate exchangeEX_for_eAcetaldehyde dehydrogenase (acetylating)ACALDAcetaldehyde reversible transportACALDtAcetaldehyde exchangeEX_acald_eAlcohol dehydrogenase (ethanol)ALCD2xFormate transport in via proton symportFORt2Formate transport via diffusionFORtiFumarate reductaseFRD7Fructose transport via PEPPyr PTS f6p generating FRUpts2D-Fructose exchangeEX_fru_eMalate transport via proton symport 2 H MALt2_222L-Malate exchangeEX_mal__L_eNADH dehydrogenase (ubiquinone-8 & 3 protons)NADH1643Succinate dehydrogenase (irreversible)SUCDiD lactate transport via proton symportD_LACt2Biomass Objective Function with GAMBIOMASS_Ecoli_core_w_GAM59.8159.814.94140.1290.36159.810.897759.810.07092.83283.5473.74781.78670.2053.5474.11823.74781.4960.51910.255713.027913.027959.81Aconitase (half-reaction A, Citrate hydro-lyase)ACONTaAconitase (half-reaction B, Isocitrate hydro-lyase)ACONTbatp_cATP3pg_c3-Phospho-D-glycerate13dpg_c3-Phospho-D-glyceroyl phosphateadp_cADPnadp_cNicotinamide adenine dinucleotide phosphate6pgc_c6-Phospho-D-gluconateco2_cCO2nadph_cNicotinamide adenine dinucleotide phosphate - reducedru5p__D_cD-Ribulose 5-phosphateo2_eO2o2_cO2nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedh_eH+h_cH+nadph_cNicotinamide adenine dinucleotide phosphate - reducednad_cNicotinamide adenine dinucleotideh2o_cH2Ofum_cFumaratemal__L_cL-Malateicit_cIsocitratenadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reducedco2_cCO2akg_c2-Oxoglutaratenad_cNicotinamide adenine dinucleotidepyr_cPyruvatecoa_cCoenzyme Aco2_cCO2accoa_cAcetyl-CoAnadh_cNicotinamide adenine dinucleotide - reducedh2o_cH2Opep_cPhosphoenolpyruvateco2_cCO2h_cH+pi_cPhosphateoaa_cOxaloacetate2pg_cD-Glycerate 2-phosphateh2o_cH2Og6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphatenh4_eAmmoniumnh4_cAmmoniumh2o_cH2Ofdp_cD-Fructose 1,6-bisphosphatepi_cPhosphatesucc_eSuccinateglx_cGlyoxylatesucc_cSuccinateatp_cATPamp_cAMPadp_cADPgln__L_eL-Glutamineq8_cUbiquinone-8q8h2_cUbiquinol-8co2_eCO2g3p_cGlyceraldehyde 3-phosphates7p_cSedoheptulose 7-phosphatee4p_cD-Erythrose 4-phosphatef6p_cD-Fructose 6-phosphateh_cH+adp_cADPatp_cATPglu__L_eL-Glutamateh_eH+glu__L_cL-Glutamateh_cH+lac__D_eD-Lactatepyr_ePyruvatexu5p__D_cD-Xylulose 5-phosphateh_eH+coa_cCoenzyme Aatp_cATPpi_cPhosphatesuccoa_cSuccinyl-CoAadp_cADPatp_cATPadp_cADPh_cH+g3p_cGlyceraldehyde 3-phosphateatp_cATPnh4_cAmmoniumgln__L_cL-Glutamineadp_cADPh_cH+pi_cPhosphatelac__D_cD-Lactatecoa_cCoenzyme Anad_cNicotinamide adenine dinucleotideco2_cCO2nadh_cNicotinamide adenine dinucleotide - reducedcoa_cCoenzyme Afor_cFormateatp_cATPadp_cADPco2_cCO2pi_ePhosphateh_eH+h_cH+pi_cPhosphateakg_e2-Oxoglutarateh_eH+h_cH+dhap_cDihydroxyacetone phosphateh_cH+h_eH+h2o_cH2Or5p_cAlpha-D-Ribose 5-phosphateaccoa_cAcetyl-CoAh2o_cH2Oh_cH+coa_cCoenzyme Api_cPhosphateactp_cAcetyl phosphatecoa_cCoenzyme Aatp_cATPh2o_cH2Opi_cPhosphateadp_cADPh_cH+nad_cNicotinamide adenine dinucleotideco2_cCO2nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reducedh_cH+6pgl_c6-phospho-D-glucono-1,5-lactoneac_eAcetateh2o_cH2Onh4_cAmmoniumh2o_cH2Opi_cPhosphateh_cH+nad_cNicotinamide adenine dinucleotidenadh_cNicotinamide adenine dinucleotide - reducedh_cH+nad_cNicotinamide adenine dinucleotidenadh_cNicotinamide adenine dinucleotide - reducedh_cH+h2o_eH2Oh2o_cH2Oco2_cCO2atp_cATPh2o_cH2Oh_cH+amp_cAMPpi_cPhosphateglc__D_eD-Glucoseh_eH+etoh_eEthanolh_cH+atp_cATPac_cAcetateadp_cADPnadph_cNicotinamide adenine dinucleotide phosphate - reducedh_cH+nadp_cNicotinamide adenine dinucleotide phosphatefum_eFumarateh_eH+h_cH+h_eH+h_cH+pep_cPhosphoenolpyruvatepyr_cPyruvateh_eH+h_cH+for_eFormateh2o_cH2Oh_cH+nad_cNicotinamide adenine dinucleotidepi_cPhosphatenadh_cNicotinamide adenine dinucleotide - reducedh_cH+h_eH+h_cH+h2o_cH2Onadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reducednh4_cAmmoniumh_cH+h_eH+pi_cPhosphateh_cH+h2o_cH2Oh2o_cH2Ocit_cCitratecoa_cCoenzyme Ah_cH+h_eH+h_cH+nadp_cNicotinamide adenine dinucleotide phosphateco2_cCO2nadph_cNicotinamide adenine dinucleotide phosphate - reducedh_eH+nad_cNicotinamide adenine dinucleotideh_cH+h_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_cH+q8_cUbiquinone-8acald_eAcetaldehydemal__L_eL-Malateacald_cAcetaldehydepep_cPhosphoenolpyruvateh_cH+pyr_cPyruvatenad_cNicotinamide adenine dinucleotidenadh_cNicotinamide adenine dinucleotide - reducedcoa_cCoenzyme Afru_eD-Fructosenadh_cNicotinamide adenine dinucleotide - reducednad_cNicotinamide adenine dinucleotideetoh_cEthanolq8h2_cUbiquinol-8h_eH+h_cH+h_eH+h_eH+h_cH+h2o_cH2Oadp_cADPglu__L_cL-Glutamateg3p_cGlyceraldehyde 3-phosphatee4p_cD-Erythrose 4-phosphateh_cH+r5p_cAlpha-D-Ribose 5-phosphateatp_cATPf6p_cD-Fructose 6-phosphatepyr_cPyruvatenad_cNicotinamide adenine dinucleotidecoa_cCoenzyme Aoaa_cOxaloacetateg6p_cD-Glucose 6-phosphatenadh_cNicotinamide adenine dinucleotide - reducedakg_c2-Oxoglutarateaccoa_cAcetyl-CoA3pg_c3-Phospho-D-glyceratepep_cPhosphoenolpyruvategln__L_cL-Glutaminenadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reducedpi_cPhosphateh2o_cH2Oacon_C_cCis-Aconitate
 
Draw the map covering the central metabolism part of the full E. coli model iJO1366:

Draw the map covering the central metabolism part of the full E. coli model iJO1366:

In [6]:
 
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism')
metabolicMap.display_in_notebook(height=escherDefaultMapHeight)
Out[6]:
Malate dehydrogenaseMDHNitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp3223NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp43L-malate transport out via proton antiport (periplasm)MALt3ppD-lactate transport via proton symport (periplasm)D_LACt2ppGlucose-1-phosphataseG1PPppTrans-aconitate methyltransferaseACONMTAcetaldehyde transport via diffusion (extracellular to periplasm)ACALDtexGlycolate oxidaseGLYCTO3Aconitate isomerase (spontaneous)ACONIsCytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp20.52Phosphoenolpyruvate carboxylasePPCFructose 6-phosphate transport via diffusion (extracellular to periplasm)F6PtexMalate synthaseMALSHydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp22Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3Ethanol reversible transport via diffusion (periplasm)ETOHtrppCytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp20.52Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp22Glycogen phosphorylaseGLCPNitrate reductase (Menaquinol-8) (periplasm)NO3R2bppNADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp43DsbA protein reoxidation reaction (aerobic)DSBAO1Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2ppCitrate synthaseCSGlucose-1-phosphate adenylyltransferaseGLGCGlycerol transport via channel (periplasm)GLYCtppGlycolate oxidaseGLYCTO4Glucose-6-phosphate isomerasePGIGlycerol transport via diffusion (extracellular to periplasm)GLYCtexQuinol monooxygenase (menaquinol 8)QMO3222Hydroxyacylglutathione hydrolaseGLYOXPhosphoglycerate kinasePGKFumarate transport via diffusion (extracellular to periplasm)FUMtexCatalaseCAT22Ethanol transport via diffusion (extracellular to periplasm)ETOHtexHydrogen transport diffusion (periplasm)H2tppSuperoxide dismutaseSPODMpp22Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5PhosphoglucomutasePGMTGlucose 6-phosphate dehydrogenaseG6PDH2rAcetyl-CoA synthetaseACSGlycerol kinaseGLYK2-oxoglutarate reversible transport via symport (periplasm)AKGt2rppMalate transport via proton symport (2 H) (periplasm)MALt2_2pp226-phosphogluconolactonasePGL(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtppDimethyl sulfoxide transport via diffusion (periplasm)DMSOtppATP synthase (four protons for one ATP) (periplasm)ATPS4rpp43NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp43Acetate kinaseACKrGlycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2Ribose-5-phosphate isomeraseRPID-xylose transport in via proton symport (periplasm)XYLt2ppD-glucose 1-phosphate transport via diffusionG1PtexMalate transport via diffusion (extracellular to periplasm)MALtexCytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp0.544Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1ppD-fructose transport via PEP:Pyr PTS (periplasm)FRUptsppPolyphosphate kinasePPK2rL-Lactate dehydrogenase (ubiquinone)L_LACD2Pyruvate kinasePYKQuinol monooxygenase (Ubiquinol-8)QMO2222L-lactate reversible transport via proton symport (periplasm)L_LACt2rppNADH dehydrogenase (menaquinone-8 & 0 protons)NADH10Glycerol dehydrogenaseGLYCDxMalate transport via proton symport (3 H) (periplasm)MALt2_3pp33Dihydroxyacetone phosphotransferaseDHAPTCO2 transport via diffusion (extracellular to periplasm)CO2texNitrate reductase (Ubiquinol-8)NO3R1bppDsbA protein reoxidation reaction (anaerobic)DSBAO2Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3PabcppPhosphoenolpyruvate carboxykinasePPCKL-lactate transport via diffusion (extracellular to periplasm)L_LACtexPyruvate dehydrogenasePDHMalic enzyme (NADP)ME2Acetaldehyde reversible transport (periplasm)ACALDtppD-fructose transport via diffusion (extracellular to periplasm)FRUtexD-xylose transport via ABC system (periplasm)XYLabcppFumarate reductaseFRD3Inorganic triphosphatasePPA2Acetate reversible transport via proton symport (periplasm)ACt2rppHydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp22Pyruvate oxidasePOXNADPH Quinone Reductase (Ubiquinone-8)NADPHQR2Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTbCitrate transport via diffusion (extracellular to periplasm)CITtexD-ribose transport via ABC system (periplasm)RIBabcppFumaraseFUM2-dehydro-3-deoxy-phosphogluconate aldolaseEDAPyruvate formate lyasePFLInorganic diphosphatasePPA2Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp22Glycogen phosphorylaseGLCP2Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1ppNADH dehydrogenase (ubiquinone-8 )NADH5D-lactate dehydrogenaseLDH_DLacaldehyde reductase (R-propane-1,2-diol forming)LCARRPhosphoglycerate mutasePGMRibulose 5-phosphate 3-epimeraseRPEFumarate reductaseFRD2NADPH Quinone Reductase (Menaquinone-8)NADPHQR3Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3PtexPhosphoenolpyruvate synthasePPS21,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7D-glucose transport via PEP:Pyr PTS (periplasm)GLCptsppTrimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp2Superoxide dismutaseSPODM22Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp22Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp33Fructose-bisphosphataseFBPHydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp22Triose-phosphate isomeraseTPI(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtexIsocitrate lyaseICLIsocitrate dehydrogenase (NADP)ICDHyrD-lactate transport via diffusion (extracellular to periplasm)D_LACtexMalate dehydrogenase (menaquinone 8 as acceptor)MDH3Formate transport via diffusion (extracellular to periplasm)FORtexEnolaseENOL-Lactate dehydrogenase (menaquinone)L_LACD3Glycerol-3-phosphataseG3PTGlucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDppD-glucose transport in via proton symport (periplasm)GLCt2ppRibokinaseRBKPhosphotransacetylasePTArGlyceraldehyde-3-phosphate dehydrogenaseGAPDCitrate transport out via proton antiport (periplasm)CITt3ppSuccinyl-CoA synthetase (ADP-forming)SUCOASHydrogen transport via diffusion (extracellular to periplasm)H2texAconitase (half-reaction A, Citrate hydro-lyase)ACONTaPhosphofructokinasePFKD-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2xAcetate transport via diffusion (extracellular to periplasm)ACtexATP maintenance requirementATPMPhosphofructokinase (s7p)PFK_3Methylglyoxal synthaseMGSANADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp22Nitrite Reductase (NADH)NTRIR2x3532Citrate transport via succinate antiport (periplasm)CITt7ppFructose 6-phosphate aldolaseF6PAMalate dehydrogenase (ubiquinone 8 as acceptor)MDH2Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6ppPyruvate reversible transport via proton symport (periplasm)PYRt2rppGlycolate oxidaseGLYCTO2TransketolaseTKT1NAD(P) transhydrogenase (periplasm)THD2pp22Succinate transport out via proton antiport (periplasm)SUCCt3ppPolyphosphate kinasePPKrAlcohol dehydrogenase (ethanol)ALCD2xSuccinate transport via diffusion (extracellular to periplasm)SUCCtexDimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x2Glycerol-3-phosphate dehydrogenase (NADP)G3PD2Xylose isomeraseXYLI1Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp2332Citrate lyaseCITLFormate transport via proton symport (uptake only, periplasm)FORt2ppGlucose transport via diffusion (extracellular to periplasm)GLCtex_copy1Pyruvate transport via diffusion (extracellular to periplasm)PYRtexSuccinate dehydrogenase (irreversible)SUCDiFormate transport via diffusion (cytoplasm to periplasm)FORtppiTransaldolaseTALATransketolaseTKT2D-xylose transport via diffusion (extracellular to periplasm)XYLtex2-Oxogluterate dehydrogenaseAKGDHAlpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtexNitrate reductase (Menaquinol-8) (periplasm)NO3R2pp22Lactoylglutathione lyaseLGTHLAldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y26-phosphogluconate dehydrataseEDDFructose-1-phosphate kinaseFRUKFormate dehydrogenase (quinone-8) (periplasm)FDH4pp2Malate oxidaseMOXCO2 transporter via diffusion (periplasm)CO2tppMalic enzyme (NAD)ME1XylulokinaseXYLKGlucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp22NAD transhydrogenaseNADTRHDGlycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6Phosphogluconate dehydrogenaseGNDHexokinase (D-glucose:ATP)HEX1Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp33Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1Fructose-bisphosphate aldolaseFBAGlucose-6-phosphate phosphataseG6PPRibose transport via diffusion (extracellular to periplasm)RIBtexFructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2ppAcetaldehyde dehydrogenase (acetylating)ACALDHCO3 equilibration reactionHCO3EFormate-hydrogen lyaseFHLGlycogen synthase (ADPGlc)GLCS1Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6PtexOxaloacetate decarboxylaseOAADCDimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2ppD-lactate dehydrogenaseLDH_D2D-lactate dehydrogenaseLDH_D2L-Lactate dehydrogenase (ubiquinone)L_LACD2D-glucose transport via PEP:Pyr PTS (periplasm)GLCptsppL-Lactate dehydrogenase (menaquinone)L_LACD3mal__L_cL-Malatenad_cNicotinamide adenine dinucleotidenadh_cNicotinamide adenine dinucleotide - reducedh_cH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteh_pH+h2o_pH2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8h_cH+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedh_cH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideh_pH+mql8_cMenaquinol 8h_pH+h_cH+mal__L_pL-Malatelac__D_pD-Lactateh_pH+lac__D_cD-Lactateh_cH+g1p_pD-Glucose 1-phosphateh2o_pH2Opi_pPhosphateglc__D_pD-Glucoseacon_T_cTrans-Aconitateamet_cS-Adenosyl-L-methionineahcys_cS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-Aconitateh_cH+o2_cO2h2o_cH2Oh_pH+pep_cPhosphoenolpyruvateh2o_cH2Oco2_cCO2h_cH+pi_cPhosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateh2o_cH2Oaccoa_cAcetyl-CoAglx_cGlyoxylateh_cH+coa_cCoenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolh_cH+o2_cO2h2o_cH2Oh_pH+h_pH+fum_pFumarateh_cH+fum_cFumaratepi_cPhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteh2o_pH2Oh_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_pH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideh_pH+h2o_pH2Otma_pTrimethylamineaccoa_cAcetyl-CoAh2o_cH2Ocit_cCitrateh_cH+coa_cCoenzyme Aatp_cATPh_cH+ppi_cDiphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2h_cH+o2s_cSuperoxide anionh2o_cH2Olgt__S_c(R)-S-Lactoylglutathioneh_cH+gthrd_cReduced glutathioneatp_cATP3pg_c3-Phospho-D-glycerateadp_cADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatenadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneh_cH+ac_cAcetateatp_cATPcoa_cCoenzyme Aamp_cAMPppi_cDiphosphateatp_cATPh_cH+glyc3p_cGlycerol 3-phosphateadp_cADPh_pH+akg_p2-Oxoglutarateh_cH+akg_c2-Oxoglutarateh_pH+h_cH+h2o_cH2O6pgc_c6-Phospho-D-gluconateh_cH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedh_cH+nad_cNicotinamide adenine dinucleotideh_pH+atp_cATPadp_cADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateh_pH+xyl__D_pD-Xylosexyl__D_cD-Xyloseh_cH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2h_cH+h2o_cH2Oh_pH+dmso_pDimethyl sulfoxideh2o_pH2Odms_pDimethyl sulfidepep_cPhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatepyr_cPyruvateatp_cATPppi_cDiphosphatepppi_cInorganic triphosphateadp_cADPlac__L_cL-Lactateq8_cUbiquinone-8q8h2_cUbiquinol-8adp_cADPh_cH+atp_cATPo2_cO2o2s_cSuperoxide anionh_cH+h_pH+lac__L_pL-Lactateh_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_cH+nad_cNicotinamide adenine dinucleotidenad_cNicotinamide adenine dinucleotidedha_cDihydroxyacetonenadh_cNicotinamide adenine dinucleotide - reducedh_cH+h_pH+h_cH+pep_cPhosphoenolpyruvatepyr_cPyruvateco2_eCO2co2_pCO2no3_pNitrateh2o_pH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)h2o_cH2Oglyc3p_pGlycerol 3-phosphateatp_cATPh_cH+pi_cPhosphateadp_cADPatp_cATPco2_cCO2adp_cADPlac__L_eL-Lactatenad_cNicotinamide adenine dinucleotidecoa_cCoenzyme Anadh_cNicotinamide adenine dinucleotide - reducedco2_cCO2nadp_cNicotinamide adenine dinucleotide phosphateco2_cCO2nadph_cNicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-Fructoseh2o_cH2Oatp_cATPadp_cADPpi_cPhosphateh_cH+2dmmql8_c2-Demethylmenaquinol 8succ_cSuccinate2dmmq8_c2-Demethylmenaquinone 8h2o_cH2Oh_cH+pi_cPhosphateh_pH+ac_pAcetateh_cH+h2_cH2h_cH+h_pH+pyr_cPyruvateh2o_cH2Oco2_cCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedh_cH+nadp_cNicotinamide adenine dinucleotide phosphateh2o_cH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-Riboseh2o_cH2Oatp_cATPpi_cPhosphateadp_cADPrib__D_cD-Riboseh_cH+h2o_cH2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphatecoa_cCoenzyme Afor_cFormateh2o_cH2Oh_cH+pi_cPhosphateno3_cNitrateh_cH+h_pH+no2_cNitriteh2o_cH2Opi_cPhosphateh_pH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineh2o_pH2Onadh_cNicotinamide adenine dinucleotide - reducedh_cH+nad_cNicotinamide adenine dinucleotidenad_cNicotinamide adenine dinucleotideh_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_cH+nadh_cNicotinamide adenine dinucleotide - reducedlald__D_cD-Lactaldehydenad_cNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphatemql8_cMenaquinol 8mqn8_cMenaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedh_cH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateatp_cATPh2o_cH2Oamp_cAMPpi_cPhosphateh_cH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatepep_cPhosphoenolpyruvatepyr_cPyruvatetmao_cTrimethylamine N-oxideh_cH+h2o_cH2Otma_cTrimethylaminefor_pFormateh_cH+co2_pCO2h_pH+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateh_pH+h_cH+h_pH+h_cH+fdp_cD-Fructose 1,6-bisphosphateh2o_cH2Opi_cPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolnadp_cNicotinamide adenine dinucleotide phosphateco2_cCO2nadph_cNicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-Lactatemqn8_cMenaquinone 8mql8_cMenaquinol 8for_eFormatefor_pFormateh2o_cH2Oh2o_cH2Opi_cPhosphateglc__D_pD-Glucoseh2o_pH2Oh_pH+glcn_pD-Gluconateh_pH+h_cH+glc__D_cD-Glucoseatp_cATPadp_cADPh_cH+pi_cPhosphatecoa_cCoenzyme Api_cPhosphatenad_cNicotinamide adenine dinucleotideh_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_pH+h_cH+coa_cCoenzyme Aatp_cATPpi_cPhosphatesuccoa_cSuccinyl-CoAadp_cADPh2_eH2atp_cATPadp_cADPh_cH+nadh_cNicotinamide adenine dinucleotide - reducedh_cH+mthgxl_cMethylglyoxalnad_cNicotinamide adenine dinucleotideac_eAcetateatp_cATPh2o_cH2Oadp_cADPh_cH+pi_cPhosphateatp_cATPs7p_cSedoheptulose 7-phosphateadp_cADPh_cH+pi_cPhosphatenadh_cNicotinamide adenine dinucleotide - reducedh_cH+nad_cNicotinamide adenine dinucleotidepi_cPhosphatepi_pPhosphatenadh_cNicotinamide adenine dinucleotide - reducedh_cH+no2_cNitritenad_cNicotinamide adenine dinucleotidenh4_cAmmoniumh2o_cH2Olac__L_cL-Lactatepyr_cPyruvatesucc_cSuccinatesucc_pSuccinateq8_cUbiquinone-8q8h2_cUbiquinol-8pi_cPhosphatepi_pPhosphateh_pH+pyr_pPyruvateh_cH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedh_pH+h_cH+atp_cATPadp_cADPnad_cNicotinamide adenine dinucleotideh_cH+nadh_cNicotinamide adenine dinucleotide - reducedsucc_eSuccinateh2o_cH2Odms_cDimethyl sulfidenad_cNicotinamide adenine dinucleotideh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedh_cH+nadp_cNicotinamide adenine dinucleotide phosphateh_cH+nadph_cNicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-Xyluloseh_pH+no2_pNitritenh4_pAmmoniumh2o_pH2Oac_cAcetateh_pH+h_cH+glc__D_eD-Glucosepyr_ePyruvateq8_cUbiquinone-8q8h2_cUbiquinol-8xyl__D_eD-Xylosenad_cNicotinamide adenine dinucleotidecoa_cCoenzyme Anadh_cNicotinamide adenine dinucleotide - reducedco2_cCO2akg_e2-Oxoglutarateh_cH+no3_cNitrateh_pH+no2_cNitriteh2o_cH2Onadp_cNicotinamide adenine dinucleotide phosphateh2o_cH2Onadph_cNicotinamide adenine dinucleotide phosphate - reducedh_cH+h2o_cH2Oatp_cATPh_cH+adp_cADPh_cH+for_pFormateco2_pCO2h_pH+o2_cO2h2o2_cHydrogen peroxideco2_cCO2nad_cNicotinamide adenine dinucleotidenadh_cNicotinamide adenine dinucleotide - reducedco2_cCO2atp_cATPh_cH+adp_cADPpi_cPhosphateg6p_pD-Glucose 6-phosphatepi_pPhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatenadp_cNicotinamide adenine dinucleotide phosphatenadph_cNicotinamide adenine dinucleotide phosphate - reducedco2_cCO2atp_cATPadp_cADPh_cH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideh2o_cH2Oh_pH+h_cH+tmao_cTrimethylamine N-oxideh_cH+h2o_cH2Otma_cTrimethylamineh2o_cH2Opi_cPhosphaterib__D_eD-Ribosepep_cPhosphoenolpyruvatepyr_cPyruvatenad_cNicotinamide adenine dinucleotidecoa_cCoenzyme Ah_cH+nadh_cNicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateh_cH+co2_cCO2h_cH+adp_cADPg6p_eD-Glucose 6-phosphateh_cH+co2_cCO2h2o_pH2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-Lactateq8h2_cUbiquinol-8q8_cUbiquinone-8pyr_cPyruvatelac__L_cL-Lactateglc__D_pD-Glucoseg6p_cD-Glucose 6-phosphatemqn8_cMenaquinone 8pyr_cPyruvatemql8_cMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
### Get the FBA model from the BiGG database

Get the FBA model from the BiGG database

 
Browse the BiGG database (http://bigg.ucsd.edu/) and download the iJO1366 metabolic model of E. coli in JSON format. Save the file in the same directory as this ipython notebook.
More information:
+ iJO1366 metabolic model article: Orth, J. D., Conrad, T. M., Na, J., Lerman, J. a, Nam, H., Feist, A. M., & Palsson, B. Ø. (2011). A comprehensive genome-scale reconstruction of Escherichia coli metabolism—2011. Molecular Systems Biology, 7(535), 1–9. http://doi.org/10.1038/msb.2011.65

Browse the BiGG database (http://bigg.ucsd.edu/) and download the iJO1366 metabolic model of E. coli in JSON format. Save the file in the same directory as this ipython notebook.

More information:

  • iJO1366 metabolic model article: Orth, J. D., Conrad, T. M., Na, J., Lerman, J. a, Nam, H., Feist, A. M., & Palsson, B. Ø. (2011). A comprehensive genome-scale reconstruction of Escherichia coli metabolism—2011. Molecular Systems Biology, 7(535), 1–9. http://doi.org/10.1038/msb.2011.65
 
### COBRApy commands

COBRApy commands

 
More information:
+ COBRApy documentation https://cobrapy.readthedocs.org/en/stable/getting_started.html
 
Load the iJO1366 model with the COBRApy package.

Load the iJO1366 model with the COBRApy package.

In [7]:
 
model = cobra.io.load_json_model('iJO1366.json')
 
The model contains the lists of reactions, metabolites, and genes, which are attributes of the cobrapy model.

The model contains the lists of reactions, metabolites, and genes, which are attributes of the cobrapy model.

In [8]:
 
print('Nb of reactions: ',len(model.reactions))
print('Nb of metabolites: ',len(model.metabolites))
print('Nb of genes: ',len(model.genes))
Nb of reactions:  2583
Nb of metabolites:  1805
Nb of genes:  1367
 
Just like a regular list, objects in the reactions, metabolites and genes lists can be retrieved by index. For example, to get the 30th reaction in the model,

Just like a regular list, objects in the reactions, metabolites and genes lists can be retrieved by index. For example, to get the 30th reaction in the model,

In [9]:
 
model.reactions[29]
Out[9]:
<Reaction EX_5dglcn_e at 0x7fd234502c88>
 
Additionally, items can be retrieved by their id using the get_by_id() function. For example, consider the reaction glucose 6-phosphate isomerase, which interconverts glucose 6-phosphate and fructose 6-phosphate. The reaction id for this reaction in our model is PGI.

Additionally, items can be retrieved by their id using the get_by_id() function. For example, consider the reaction glucose 6-phosphate isomerase, which interconverts glucose 6-phosphate and fructose 6-phosphate. The reaction id for this reaction in our model is PGI.

In [10]:
 
pgi = model.reactions.get_by_id("PGI")
 
With an interactive shell such as IPython, reactions can also be retrieved using tab-completion to list elements inside a list. While this is not recommended behavior for most code because of the possibility for characters like “-” inside ids, this is very useful while in an interactive prompt. Start typing `model.reactions.`, then the first characters of the reaction name, and hit tab to get a list of reactions.

With an interactive shell such as IPython, reactions can also be retrieved using tab-completion to list elements inside a list. While this is not recommended behavior for most code because of the possibility for characters like “-” inside ids, this is very useful while in an interactive prompt. Start typing model.reactions., then the first characters of the reaction name, and hit tab to get a list of reactions.

In [11]:
 
pgi = model.reactions.PGI
 
We can view the full name, reaction equation and metabolites with stochiometry as strings.

We can view the full name, reaction equation and metabolites with stochiometry as strings.

In [12]:
 
print(pgi.name)
print(pgi.reaction)
print(pgi.metabolites)
Glucose-6-phosphate isomerase
g6p_c <=> f6p_c
{<Metabolite f6p_c at 0x7fd236444cc0>: 1.0, <Metabolite g6p_c at 0x7fd23641d5f8>: -1.0}
 
We can also view reaction upper and lower bounds. Because the pgi.lower_bound < 0, and pgi.upper_bound > 0, pgi is reversible

We can also view reaction upper and lower bounds. Because the pgi.lower_bound < 0, and pgi.upper_bound > 0, pgi is reversible

In [13]:
 
print(pgi.lower_bound, "< pgi <", pgi.upper_bound)
print(pgi.reversibility)
-1000.0 < pgi < 1000.0
True
 
We define a function to print out the most relevant information about a gene in a cobra model.

We define a function to print out the most relevant information about a gene in a cobra model.

In [14]:
 
def print_gene_info(gene):
    print("cobra_id: ",gene.id)
    print("name: ",gene.name)
    print("associated reactions:")
    for reac in gene.reactions:
        print(reac.id, ', ', reac.name)
    print()
 
Try the print function with one gene of the model.

Try the print function with one gene of the model.

In [15]:
 
print_gene_info(model.genes.b0841)
cobra_id:  b0841
name:  ybjG
associated reactions:
UDCPDP ,  Undecaprenyl-diphosphatase
UDCPDPpp ,  Undecaprenyl-diphosphatase (periplasm)

 
### FBA solution

FBA solution

In [16]:
 
solution = model.optimize()
 
Simulations using flux balance analysis can be solved using Model.optimize(). This will maximize or minimize (maximizing is the default) flux through the objective reactions. The Model.optimize() function will return a Solution object, which will also be stored at model.solution. A solution object has several attributes:
+ f: the objective value
+ status: the status from the linear programming solver
+ x_dict: a dictionary of {reaction_id: flux_value} (also called "primal")
+ x: a list for x_dict
+ y_dict: a dictionary of {metabolite_id: dual_value}.
+ y: a list for y_dict
For example, after the last call to model.optimize(), the status should be 'optimal' if the solver returned no errors, and f should be the objective value

Simulations using flux balance analysis can be solved using Model.optimize(). This will maximize or minimize (maximizing is the default) flux through the objective reactions. The Model.optimize() function will return a Solution object, which will also be stored at model.solution. A solution object has several attributes:

  • f: the objective value
  • status: the status from the linear programming solver
  • x_dict: a dictionary of {reaction_id: flux_value} (also called "primal")
  • x: a list for x_dict
  • y_dict: a dictionary of {metabolite_id: dual_value}.
  • y: a list for y_dict

For example, after the last call to model.optimize(), the status should be 'optimal' if the solver returned no errors, and f should be the objective value

In [17]:
 
print('Satus: ',solution.status)
print('Growth rate: %.2f' % solution.f)
Satus:  optimal
Growth rate: 0.98
 
### Maximum aerobic growth rate
We want to calculate the maximum aerobic growth of E. coli under the assumption that uptake of glucose, and not oxygen, is the limiting constraint on growth (aerobic conditions).

Maximum aerobic growth rate

We want to calculate the maximum aerobic growth of E. coli under the assumption that uptake of glucose, and not oxygen, is the limiting constraint on growth (aerobic conditions).

 
First we set the maximum glucose uptake rate to 18.5 mmol gDW<sup>-1</sup> h<sup>-1</sup> (millimoles per gram dry cell weight per hour, the default flux units used in the COBRA package). Knowing that the glucose exchange reaction id is `EX_glc__D_e`, print the reactions name, reaction equation, list of metabolites and lower and upper bounds. Then, set the new value of the lower bound to -18.5.
By convention, exchange reactions are written as export reactions (e.g. `glc__D_e <==>`), so import of a metabolite is a negative flux. Maximum uptake rates are therefore expressed as the negative lower bounds of the corresponding exchange reaction with units [mmol gDW<sup>-1</sup> h<sup>-1</sup>].

First we set the maximum glucose uptake rate to 18.5 mmol gDW-1 h-1 (millimoles per gram dry cell weight per hour, the default flux units used in the COBRA package). Knowing that the glucose exchange reaction id is EX_glc__D_e, print the reactions name, reaction equation, list of metabolites and lower and upper bounds. Then, set the new value of the lower bound to -18.5.

By convention, exchange reactions are written as export reactions (e.g. glc__D_e <==>), so import of a metabolite is a negative flux. Maximum uptake rates are therefore expressed as the negative lower bounds of the corresponding exchange reaction with units [mmol gDW-1 h-1].

In [18]:
 
glc_exchange = model.reactions.get_by_id('EX_glc__D_e')
print(glc_exchange.name)
print(glc_exchange.reaction)
print(glc_exchange.metabolites)
print(glc_exchange.lower_bound, "< EX_glc__D_e <", glc_exchange.upper_bound)
glc_exchange.lower_bound = -18.5
print(glc_exchange.lower_bound, "< EX_glc__D_e <", glc_exchange.upper_bound)
D-Glucose exchange
glc__D_e <=> 
{<Metabolite glc__D_e at 0x7fd2362ee860>: -1.0}
-10.0 < EX_glc__D_e < 1000.0
-18.5 < EX_glc__D_e < 1000.0
 
Second we allow unlimited oxygen uptake. Search the id of the oxygen (O2) uptake reaction of the iJO1366 model in the BiGG database. Change the lower bound of the oxygen uptake reaction to -1000. By setting the lower bound of the oxygen uptake reaction to such a large negative number, it is practically unbounded.

Second we allow unlimited oxygen uptake. Search the id of the oxygen (O2) uptake reaction of the iJO1366 model in the BiGG database. Change the lower bound of the oxygen uptake reaction to -1000. By setting the lower bound of the oxygen uptake reaction to such a large negative number, it is practically unbounded.

In [19]:
 
o2_exchange = model.reactions.get_by_id('EX_o2_e')
print(o2_exchange.name)
print(o2_exchange.reaction)
print(o2_exchange.metabolites)
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
o2_exchange.lower_bound = -1000
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
O2 exchange
o2_e <=> 
{<Metabolite o2_e at 0x7fd2362f57f0>: -1.0}
-1000.0 < EX_o2_e < 1000.0
-1000 < EX_o2_e < 1000.0
 
The objective function is determined from the objective_coefficient attribute of the objective reaction(s). In the iJO1366 model, there are two possible objective reactions, the “core” and “wild-type” biomass reactions. These are reactions that drain biomass precursor compounds in experimentally determined ratios to simulate growth. The “wild- type” biomass reaction contains the precursors to all the typical wild-type cellular components of E. coli, while the “core” biomass reaction contains the precursors only to essential components.
We can find the id's of these reactions by searching for the string "biomass" in the reaction names.

The objective function is determined from the objective_coefficient attribute of the objective reaction(s). In the iJO1366 model, there are two possible objective reactions, the “core” and “wild-type” biomass reactions. These are reactions that drain biomass precursor compounds in experimentally determined ratios to simulate growth. The “wild- type” biomass reaction contains the precursors to all the typical wild-type cellular components of E. coli, while the “core” biomass reaction contains the precursors only to essential components.

We can find the id's of these reactions by searching for the string "biomass" in the reaction names.

In [20]:
 
for reac in model.reactions:
    if re.search('biomass', reac.name, re.I):
        print(reac.name, ', id:', reac.id)
E. coli biomass objective function (iJO1366) - WT - with 53.95 GAM estimate , id: BIOMASS_Ec_iJO1366_WT_53p95M
E. coli biomass objective function (iJO1366) - core - with 53.95 GAM estimate , id: BIOMASS_Ec_iJO1366_core_53p95M
 
Next, we set the objective function as the core biomass reaction, which contains the precursors only to essential components. The objective function can be set to a specific reaction by using the `model.change_objective` function.

Next, we set the objective function as the core biomass reaction, which contains the precursors only to essential components. The objective function can be set to a specific reaction by using the model.change_objective function.

In [21]:
 
model.change_objective('BIOMASS_Ec_iJO1366_core_53p95M')
In [22]:
 
print(model.reactions.BIOMASS_Ec_iJO1366_WT_53p95M.reaction)
0.18569 k_c + 0.003805 pg161_p + 0.025612 dgtp_c + 5.5e-05 udcpdp_c + 0.437778 leu__L_c + 7e-06 mobd_c + 0.154187 glycogen_c + 7e-06 mococdp_c + 0.024732 pe161_p + 2e-06 btn_c + 0.000223 pydx5p_c + 0.001345 murein3p3p_p + 0.129799 ctp_c + 0.009618 pe161_c + 0.234232 asp__L_c + 0.000605 murein3px4p_p + 0.255712 glu__L_c + 0.004957 pe181_c + 0.000223 amet_c + 0.005381 murein4p4p_p + 0.000223 hemeO_c + 0.000223 2dmmql8_c + 0.000223 ribflv_c + 48.752916 h2o_c + 0.000673 murein4px4px4p_p + 0.001961 pg181_p + 0.004439 pg161_c + 0.209121 gtp_c + 0.002288 pg181_c + 0.031798 pe160_p + 0.000223 thf_c + 0.012379 nh4_c + 0.005448 murein4px4p_p + 0.000112 nadp_c + 0.214798 pro__L_c + 0.000335 nadph_c + 0.000223 thmpp_c + 0.234232 asn__L_c + 0.000674 cu2_c + 0.000307 ni2_c + 0.246506 thr__L_c + 0.002944 clpn160_p + 0.180021 phe__L_c + 0.000223 pheme_c + 0.024805 dttp_c + 3e-06 lipopb_c + 0.008253 mg2_c + 0.333448 lys__L_c + 0.03327 ptrc_c + 0.012747 pe181_p + 0.000223 10fthf_c + 0.140101 utp_c + 0.000223 adocbl_c + 0.411184 val__L_c + 0.024805 datp_c + 0.005707 pg160_c + 3.1e-05 malcoa_c + 0.008151 colipa_e + 0.209684 ser__L_c + 0.000223 chor_c + 0.28742 arg__L_c + 0.004952 ca2_c + 0.092056 his__L_c + 0.088988 cys__L_c + 0.000168 coa_c + 0.000223 gthrd_c + 0.000223 5mthf_c + 0.255712 gln__L_c + 7e-06 mocogdp_c + 0.00118 clpn181_p + 0.000223 enter_c + 2.5e-05 2fe2s_c + 54.119975 atp_c + 0.000279 accoa_c + 0.000324 zn2_c + 0.000658 mn2_c + 0.004126 so4_c + 0.006744 spmd_c + 0.595297 gly_c + 0.004952 cl_c + 0.000248 4fe4s_c + 0.000223 fad_c + 0.025612 dctp_c + 0.004892 pg160_p + 0.000116 bmocogdp_c + 0.149336 met__L_c + 0.499149 ala__L_c + 9.8e-05 succoa_c + 2.4e-05 cobalt2_c + 0.055234 trp__L_c + 0.006388 fe2_c + 0.001787 nad_c + 0.007428 fe3_c + 0.012366 pe160_c + 0.282306 ile__L_c + 0.000223 mlthf_c + 0.000223 q8h2_c + 0.00229 clpn161_p + 0.000223 sheme_c + 0.000223 mql8_c + 0.133993 tyr__L_c + 4.5e-05 nadh_c --> 0.749831 ppi_c + 53.95 h_c + 53.95 adp_c + 53.945874 pi_c
 
Perform FBA with maximization of the biomass reaction as the objective.

Perform FBA with maximization of the biomass reaction as the objective.

In [23]:
 
solution = model.optimize()
 
Growth rate of the optimal solution.

Growth rate of the optimal solution.

In [24]:
 
print('Aerobic conditions.')
print('Satus: ',solution.status)
print('Growth rate: %.2f' % solution.f)
Aerobic conditions.
Satus:  optimal
Growth rate: 1.83
 
The optimal fluxes accross all reactions can be inspected by printing the attribute x_dict.

The optimal fluxes accross all reactions can be inspected by printing the attribute x_dict.

In [25]:
 
solution.x_dict
Out[25]:
{'EX_acmana_e': 0.0,
 'EX_cys__D_e': 0.0,
 'FEOXAMR3': 0.0,
 'GPDDA1pp': 0.0,
 'FECRMtonex': 0.0,
 'IPPMIb': -0.8237928684068265,
 'TMAOR2': 0.0,
 'ACGAMT': 0.0,
 'DCYTD': 0.0,
 'O16AUNDtpp': 0.0,
 'POAACR': 0.0,
 'EX_f6p_e': 0.0,
 'FEOXAMUtpp': 0.0,
 'PGPP181': 0.0,
 'EX_cynt_e': 0.0,
 'PGPP180pp': 0.0,
 'XYLtex': 0.0,
 'EX_gam_e': 0.0,
 'HOMtex': 0.0,
 'TTDCAtexi': 0.0,
 'OGMEACPD': 3.6569863934195786e-06,
 '3OAS120': 0.0,
 'TDSR1': 0.0,
 'MDH3': 0.0,
 'DDCAtexi': 0.0,
 'OCBT': 0.5408536596411295,
 'R15BPK': 998.39344016504,
 'TRPS3': 0.1039370387805745,
 'EX_LalaDglu_e': 0.0,
 'ARGTRS': 0.0,
 'DKGLCNR2y': 0.0,
 'NADDP': 0.0,
 'GMAND': 0.0,
 '2AGPE181tipp': 0.0,
 'SELGTHR3': 0.0,
 'G6Pt6_2pp': 0.0,
 'EX_ser__D_e': 0.0,
 '4HTHRS': 0.0,
 'FACOAL140t2pp': 0.0,
 'ALLabcpp': 0.0,
 'UDCPDPS': 0.00010056712581903744,
 'EX_23cump_e': 0.0,
 'PGP141abcpp': 0.0,
 'EX_doxrbcn_e': 0.0,
 'ASP1DC': 0.0010532120812911734,
 'GLNabcpp': 0.0,
 'LPLIPAL2ATE160': 0.0,
 'ASNN': 0.0,
 'ASNabcpp': 0.0,
 'CLPNS161pp': 0.0,
 'DGK1': 0.0,
 'NI2tpp': 0.0005906033025372617,
 'AMAOTr': 3.6569863368640654e-06,
 'FLVRx': 0.0,
 'PAPA181pp': 0.0,
 'EX_glc__D_e': -18.5,
 'BIOMASS_Ec_iJO1366_WT_53p95M': 0.0,
 'EX_inost_e': 0.0,
 'SHKK': 0.696873498636819,
 'GARFT': 0.8151148396945018,
 'AACPS4': 0.2750565745946601,
 'METDabcpp': 0.0,
 'EX_quin_e': 0.0,
 'EX_fruur_e': 0.0,
 'SUCASPtpp': 0.0,
 '3OAR161': 0.0,
 'SADH': 0.0,
 'SUCOAS': -5.8448069735873105,
 'EX_xan_e': 0.0,
 'LYSt3pp': 0.0,
 'CGLYabcpp': 0.0,
 'MN2t3pp': 0.0,
 'NTD6': 0.0,
 'BTS5': 3.6569863934195786e-06,
 'DURIPP': 0.0,
 'ASPTRS': 0.0,
 'EX_imp_e': 0.0,
 'CMPtex': 0.0,
 'SO2tpp': 0.0,
 'FACOAE141': 0.0,
 'L_LACt2rpp': 0.0,
 'EX_udpglcur_e': 0.0,
 'EX_hom__L_e': 0.0,
 'GLYCLTDy': 0.0,
 'EX_indole_e': 0.0,
 'XYLt2pp': 0.0,
 'EX_eca4colipa_e': 0.0,
 'EX_hxan_e': 0.0,
 'EX_mnl_e': 0.0,
 'HCO3E': 0.96150400502313,
 'ADK4': 0.0,
 'EX_progly_e': 0.0,
 'EX_tyrp_e': 0.0,
 'GLYt2pp_copy1': 1000.0,
 'FEENTERR1': 0.0,
 'AGM3PA': 0.0,
 'PSSA141': 0.0,
 '3HAD60': 0.0,
 'GPDDA2pp': 0.0,
 'ALR4x': 0.0,
 'EX_xylu__L_e': 0.0,
 'AKGDH': 6.804509912812353,
 '2AGPEAT141': 0.0,
 '23CCMPtex': 0.0,
 'G3PAT181': 0.0,
 'S4FE4SR': 0.0,
 'HEPT1': 0.0,
 '2AGPG120tipp': 0.0,
 'PGSA160': 0.0,
 'PLIPA1A141pp': 0.0,
 'PGP161abcpp': 0.0,
 'EX_g3pc_e': 0.0,
 '3OAS160': 0.0,
 'EX_fe3hox_un_e': 0.0,
 '12DGR180tipp': 0.0,
 '3OAS100': 0.0,
 'TARTRDtex': 0.0,
 'HXPRT': 0.0,
 'SBTtex': 0.0,
 'CD2tpp': 0.0,
 'LPLIPAL2ATE120': 0.0,
 'MDH2': 0.0,
 'EX_gam6p_e': 0.0,
 'EX_udpg_e': 0.0,
 'MCITD': 0.0,
 'EX_tym_e': 0.0,
 'G3PEtex': 0.0,
 'HYXNtpp': 0.0,
 'EX_gly_e': 0.0,
 'CLIPAabctex': 0.0,
 'PPC': 5.4111659696287875,
 'EX_val__L_e': 0.0,
 'THZPSN3': 0.00040775398286629905,
 'RNTR3c2': 0.049400400695508356,
 'ALAALAr': 0.05081016895019275,
 'APH141': 0.0,
 'ASPCT': 0.6048564070056273,
 'FDMO2': 0.0,
 'MALTTTRtexi': 0.0,
 'ACACt2pp': 0.0,
 'PPPGO3': 0.0004077539828662834,
 'ARGabcpp': 0.0,
 'EX_gsn_e': 0.0,
 'URIK2': 0.0,
 'BUTt2rpp': 0.0,
 '3NTD4pp': 0.0,
 'EX_lys__L_e': 0.0,
 'AM4PCP': 0.0,
 'ACPPAT140': 0.0,
 'CYNTtex': 0.0,
 'TRDR': -1.3877787807814457e-17,
 'SELtpp': 0.0,
 'EX_tmao_e': 0.0,
 'R5PP': 0.0,
 'PPCSCT': 0.0,
 'GLYK': 0.0,
 '12DGR140tipp': 0.0,
 'NADH10': 0.0,
 'PLIPA1A140pp': 0.0,
 'ACPS1': 0.0,
 'EX_cu_e': 0.0,
 '4HOXPACDtex': 0.0,
 'EX_orn_e': 0.0,
 'EX_ttdca_e': 0.0,
 'Kabcpp': 0.0,
 'EAR181y': 0.0,
 'G3PGtex': 0.0,
 'EX_halipa_e': 0.0,
 'TMAtex': 0.0,
 'ARBTNR3': 0.0,
 'OMPHHX3': 0.0,
 'GLCDpp': 0.0,
 'DALAtex': 0.0,
 'GCALDD': 0.0012232619485993109,
 'MCOATA': 0.14230796851347804,
 'SUCTARTtpp': 0.0,
 'PYDXPP': 0.0,
 'ACOAD2f': -0.650724158845037,
 'LPLIPAL2ATE141': 0.0,
 'EX_malthx_e': 0.0,
 'O16AT': 0.0,
 'EX_ura_e': 0.0,
 '2AGPEAT120': 0.0,
 'F6Pt6_2pp': 0.0,
 'XMPtex': 0.0,
 'ICHORT': 0.0,
 'AACTOOR': 0.0,
 'TRPTRS': 0.0,
 'FORCT': 0.0,
 'GUR1PPpp': 0.0,
 'PRAIi': 0.1039370387805745,
 'SKMt2pp': 0.0,
 'HYPOE': 0.0,
 'HEX4': 0.0,
 'ACGK': 0.5408536596411295,
 'FCI': 0.0,
 'QMO3': 0.0,
 'HMBS': 0.0008155079657325662,
 'GDPDPK': 0.0,
 '12PPDStpp': 0.0,
 'MALt2_3pp': 0.0,
 'HXCT': 0.0,
 'EX_pi_e': -1.7638212208323694,
 'ACODA': 0.5408536596411295,
 'PLIPA2A180pp': 0.0,
 'BALAt2pp': 0.0,
 'EX_hdcea_e': 0.0,
 'PAPSR2': 0.453232265654835,
 'PTRCORNt7pp': 0.0,
 'INSK': 0.0,
 'ACOAD5f': -0.650724158845037,
 'EX_tartr__D_e': 0.0,
 'EX_chol_e': 0.0,
 'LIPAHT2ex': 0.0,
 'K2L4Aabctex': 0.03557516363518565,
 'ADSK': 0.453232265654835,
 'GALCTtex': 0.0,
 'XANt2pp': 0.0,
 'CPGNUtex': 0.0,
 'HKNDDH': 0.0,
 'EX_malt_e': 0.0,
 'GART': 0.0044852938115294595,
 'PETNT161pp': 0.0,
 'PRFGS': 0.8196001335060146,
 'I2FE2ST': 5.119780950788022e-05,
 'GLCATr': 0.0,
 'UDCPDP': 0.050810168950171604,
 'ANPRT': 0.1039370387805745,
 'DM_4crsol_c': 0.00040775398286629905,
 'EX_metsox_R__L_e': 0.0,
 'ACGAM1PPpp': 0.0,
 'EX_ser__L_e': 0.0,
 'H2Otex': -84.23337926378917,
 'ALDD2y': 0.0,
 'EX_5mtr_e': 0.0,
 'ARGt3pp': 0.0,
 'GAMtex': 0.0,
 'VALt2rpp': 0.0,
 'GLYCLTDx': 0.0,
 'EAR180y': 0.0,
 'EX_fe3hox_e': 0.0,
 'LPLIPAL1G141pp': 0.0,
 'ADK3': -1000.0,
 'MNNH': 0.0,
 'PDX5PS': 0.0004077539829268062,
 'IPMD': 0.8237928684068578,
 'ICYSDS': 0.0033004302200611104,
 'PSD140': 0.0,
 'APG3PAT180': 0.0,
 'ARGtex': 0.0,
 'DAPabcpp': 0.0,
 'CFAS180E': 0.0,
 'AGPAT181': 0.0,
 'MALDDH': 0.0,
 'ACOAD8f': 0.0,
 'PAPA180': 0.0,
 'EX_cbl1_e': 0.0,
 'NADK': 0.0008173364589282151,
 'THRt2pp': 0.0,
 'CPGNtonex': 0.0,
 'PAPA180pp': 0.0,
 'NI2abcpp': 0.0,
 'RNDR4b': 0.0,
 'SDPTA': -0.6782777228263512,
 '3HAD160': 0.0,
 'NTD7pp': 0.0,
 'TALA': 2.216954116917009,
 'TAURtex': 0.0,
 'CPGNR3': 0.0,
 'AM4PA': 0.0,
 'EX_ala__L_e': 0.0,
 'PLIPA1E141pp': 0.0,
 'DHMPTR': 0.0,
 'GALCTt2rpp': 0.0,
 'FE2abcpp': 0.0,
 'HACD4': 0.650724158845037,
 'LPLIPAL1A120pp': 0.0,
 'SLNTtex': 0.0,
 'NADPPPS': 0.0,
 'MALTPTabcpp': 0.0,
 'NO3R1pp': 0.0,
 'EX_thm_e': 0.0,
 'APG3PAT160': 0.0,
 'AMALT4': 0.0,
 'TKT2': 1.519672864297263,
 '23DAPPAt2pp': 0.0,
 'PSSA161': 0.13752828729733005,
 'G5SD': 0.4041975635986823,
 'IGPS': 0.1039370387805745,
 'CYTDtex': 0.0,
 'SHSL1': 0.28142521639880025,
 'MNLtex': 0.0,
 'ETHAtex': 0.0,
 '12PPDRtpp': 0.0,
 'DAMPtex': 0.0,
 'DHNPTE': 0.0,
 'ALATA_L': 998.1632456710274,
 'G3PCtex': 0.0,
 'BUTSO3abcpp': 0.0,
 'COLIPAabctex': 0.0,
 'NOtex': 0.0,
 'PGPP180': 0.0,
 'NAtex': 0.0,
 'XTSNt2rpp': 0.0,
 'ALCD2x': 0.0,
 'EX_csn_e': 0.0,
 'FACOAL60t2pp': 0.0,
 'ADOCBIK': 0.0,
 'G3PD5': 0.0,
 'MNt2pp': 0.0,
 'AACPS2': 0.0,
 'EX_cobalt2_e': -4.5712329892921844e-05,
 'ALPATE160pp': 0.0,
 'EX_psclys_e': 0.0,
 'GLYCLTtex': 0.0,
 'PYRt2rpp': 0.0,
 'FUCtpp': 0.0,
 'OCTNLL': 0.0,
 'PA181abcpp': 0.0,
 'EX_butso3_e': 0.0,
 'TARTD': 0.0,
 'IDONtex': 0.0,
 'EX_btn_e': 0.0,
 'NADH18pp': 0.0,
 'LPLIPAL2A181': 0.0,
 'ALPATG160pp': 0.0,
 'THRAi': 0.0,
 '3OAR180': 0.0,
 'PGLYCP': 0.0,
 'NADH9': 0.0,
 'PGPP140pp': 0.0,
 'OHPHM': 2.168404344971009e-19,
 'PLIPA1A161pp': 0.0,
 'FBA': 12.87801450141012,
 'NADPHQR2': 0.0,
 'AGM4Pt2pp': 0.0,
 'MN6PP': 0.0,
 'PDH': 14.561773447795868,
 'EX_34dhpac_e': 0.0,
 'MLTP2': 0.0,
 'CGLYtex': 0.0,
 'EX_adocbl_e': 0.0,
 'NTPP6': 0.0,
 'ECOAH5': 0.650724158845037,
 'KARA2': 0.5312302999468557,
 'NTP12': 0.0,
 'UGLT': 0.0,
 'EX_26dap__M_e': 0.0,
 'PLIPA2A140pp': 0.0,
 'FUMt2_3pp': 0.0,
 'G6PDA': 0.0,
 'PLIPA1E181pp': 0.0,
 'PAPA161': 0.0,
 'EAR80y': 0.0,
 'GLYt4pp': 0.0,
 'MDDCP1pp': 0.0,
 'GLCNtex': 0.0,
 'NOVBCNtpp': 0.0,
 'PGPP120': 0.0,
 'RFAMPtex': 0.0,
 'AGM3PApp': 0.0,
 'FRUtex': 0.0,
 'DHCINDO': 0.0,
 'EX_feoxam_e': 0.0,
 'UPLA4FNT': 0.0,
 'HPPK2': 0.0012232619485993109,
 'KDOCT2': 0.0711503272703713,
 'SERtex': 0.0,
 'HEPK1': 0.0,
 'PLIPA1G181pp': 0.0,
 'LPLIPAL2G141': 0.0,
 'PLIPA2E161pp': 0.0,
 'COLIPAabcpp': 0.0,
 'DHQS': 0.696873498636819,
 'NTD1': 0.0,
 'PYAM5PO': 0.0,
 'EX_for_e': 0.0,
 'FRULYSDG': 0.0,
 'SPMDt3pp': 0.0,
 'EX_ddca_e': 0.0,
 'TDPADGAT': 0.0,
 'MANGLYCtex': 0.0,
 'DADA': 0.0,
 '12DGR181tipp': 0.0,
 'BTNtex': 0.0,
 'GLUDy': -15.636738983999862,
 'UAAGDS': 0.050810168950171604,
 'SUCCt2_2pp': 0.0,
 'PEAMNOpp': 0.0,
 'SULFACtex': 0.0,
 'FACOAE160': 0.23336692970967687,
 'EX_dimp_e': 0.0,
 'HISt2rpp': 0.0,
 'PROGLYtex': 0.0,
 'FEENTERexs': 0.0,
 'PE180abcpp': 0.0,
 'GAL1Ptex': 0.0,
 'NADS1': 0.004165307502103684,
 'FE3HOXtonex': 0.0,
 'PGSA120': 0.0,
 'GALT1': 0.0,
 'GTPHs': 0.0,
 'TYRL': 0.00040775398286629905,
 'NOVBCNtex': 0.0,
 'ACt4pp': 0.0,
 'PSD161': 0.13752828729733005,
 'CCGS': 0.0,
 'MLDEP1pp': 0.0,
 'DAGK160': 0.0,
 'TREH': 0.0,
 'ASPO6': 0.004165307502103684,
 'ACGS': 0.5408536596411295,
 'GALURt2rpp': 0.0,
 'EX_glyald_e': 0.0,
 '3GMPtex': 0.0,
 'PA161abcpp': 0.0,
 'ACGAL1PPpp': 0.0,
 'EAR141x': 0.0,
 'RBK': 0.0,
 'G1PPpp': 0.0,
 'EDD': 0.0,
 'GK1': 0.4456330479292774,
 'LPLIPAL1G161pp': 0.0,
 'GLYCL': 0.09984395675950841,
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Draw the fluxes on the metabolic map. We observe that there is high flux in the glycolysis, pentose phosphate, TCA cycle, and oxidative phosphorylation pathways,

Draw the fluxes on the metabolic map. We observe that there is high flux in the glycolysis, pentose phosphate, TCA cycle, and oxidative phosphorylation pathways,

In [26]:
 
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
Out[26]:
Malate dehydrogenaseMDH 8.71Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp 0.0033NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 5.41Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 0.00122Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 0.00Ethanol reversible transport via diffusion (periplasm)ETOHtrpp 0.00Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 0.00DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 8.77Glucose-1-phosphate adenylyltransferaseGLGC 0.00Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 10.8Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK -30.0Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex 0.00Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 0.00Glucose 6-phosphate dehydrogenaseG6PDH2r 7.73Acetyl-CoA synthetaseACS 994Glycerol kinaseGLYK 0.002-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 7.73(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp 10243NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 56.7Acetate kinaseACKr -993Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI -3.92D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 64.10.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 0.00Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx 0.00Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 1.45CO2 transport via diffusion (extracellular to periplasm)CO2tex -35.9Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 0.00L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 14.6Malic enzyme (NADP)ME2 0.00Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 0.00Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp 0.00Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 8.77Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 8.712-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 0.00Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 0.00Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM -26.9Ribulose 5-phosphate 3-epimeraseRPE 3.74Fumarate reductaseFRD2 0.00NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 0.001,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 18.5Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 0.00Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.00Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI 14.1(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 0.00Isocitrate dehydrogenase (NADP)ICDHyr 8.77D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex 0.00EnolaseENO 26.9L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 993Glyceraldehyde-3-phosphate dehydrogenaseGAPD 30.0Citrate transport out via proton antiport (periplasm)CITt3pp 0.00Succinyl-CoA synthetase (ADP-forming)SUCOAS -5.84Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 8.77PhosphofructokinasePFK 12.9D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex 0.00ATP maintenance requirementATPM 3.15Phosphofructokinase (s7p)PFK_3 0.00Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.00Fructose 6-phosphate aldolaseF6PA 1.45Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp 0.00Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 0.00Glycolate oxidaseGLYCTO2 0.00122TransketolaseTKT1 2.22NAD(P) transhydrogenase (periplasm)THD2pp 0.0022Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.00Polyphosphate kinasePPKr -1.00e+3Alcohol dehydrogenase (ethanol)ALCD2x 0.00Succinate transport via diffusion (extracellular to periplasm)SUCCtex 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 -0.254Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 0.0033Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 18.5Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 0.00Succinate dehydrogenase (irreversible)SUCDi 6.81Formate transport via diffusion (cytoplasm to periplasm)FORtppi 0.00TransaldolaseTALA 2.22TransketolaseTKT2 1.52D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 6.80Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 0.00Malate oxidaseMOX 0.00297CO2 transporter via diffusion (periplasm)CO2tpp -35.9Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 7.73Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA 12.9Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD -3.41e-13HCO3 equilibration reactionHCO3E 0.962Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 0.00Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 18.5L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
### Maximum anaerobic growth rate
In order to simulate anaerobic conditions, we set the lower bound of the oxygen uptake reaction to zero, such that no oxygen can enter the system.

Maximum anaerobic growth rate

In order to simulate anaerobic conditions, we set the lower bound of the oxygen uptake reaction to zero, such that no oxygen can enter the system.

In [27]:
 
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
o2_exchange.lower_bound = 0
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
-1000 < EX_o2_e < 1000.0
0 < EX_o2_e < 1000.0
 
Perform FBA with maximization of the biomass reaction as the objective.

Perform FBA with maximization of the biomass reaction as the objective.

In [28]:
 
solution = model.optimize()
print('Anaerobic conditions.')
print('Satus: ',solution.status)
print('Growth rate: %.2f' % solution.f)
Anaerobic conditions.
Satus:  optimal
Growth rate: 0.48
 
When `model.optimize()` is used as before, the resulting growth rate is now much lower, 0.48 hr^-1.

When model.optimize() is used as before, the resulting growth rate is now much lower, 0.48 hr^-1.

 
Draw the fluxes on the metabolic map. The flux distribution shows that oxidative phosphorylation is not used in these conditions, and that acetate, formate, and ethanol are produced by fermentation pathways

Draw the fluxes on the metabolic map. The flux distribution shows that oxidative phosphorylation is not used in these conditions, and that acetate, formate, and ethanol are produced by fermentation pathways

In [29]:
 
metabolicMap.reaction_data=solution.x_dict
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
Out[29]:
Malate dehydrogenaseMDH 0.340Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp 0.0033NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 1.57Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 0.00Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 3.49Ethanol reversible transport via diffusion (periplasm)ETOHtrpp -14.7Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 13.0Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 0.00DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 0.512Glucose-1-phosphate adenylyltransferaseGLGC 13.0Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 18.5Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK -35.9Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex -14.7Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 1.14e-13Glucose 6-phosphate dehydrogenaseG6PDH2r 0.00Acetyl-CoA synthetaseACS 985Glycerol kinaseGLYK -4.11e-182-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 0.00(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp -12.243NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 0.00Acetate kinaseACKr -1.00e+3Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI -0.351D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 0.000.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 0.00Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx 0.00Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 14.6CO2 transport via diffusion (extracellular to periplasm)CO2tex 0.174Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 0.00L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 0.00Malic enzyme (NADP)ME2 0.00Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 0.00Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp -15.0Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 0.512Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 0.3392-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 31.7Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 0.00Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM -35.1Ribulose 5-phosphate 3-epimeraseRPE -0.370Fumarate reductaseFRD2 0.158NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 0.001,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 18.5Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 0.00Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.00Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI 18.0(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 0.00Isocitrate dehydrogenase (NADP)ICDHyr 0.512D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex -31.6EnolaseENO 35.1L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 1.00e+3Glyceraldehyde-3-phosphate dehydrogenaseGAPD 35.9Citrate transport out via proton antiport (periplasm)CITt3pp 0.00Succinyl-CoA synthetase (ADP-forming)SUCOAS 0.250Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 0.512PhosphofructokinasePFK 0.00D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex -15.0ATP maintenance requirementATPM 3.15Phosphofructokinase (s7p)PFK_3 3.49Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.00Fructose 6-phosphate aldolaseF6PA 14.6Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp 6.41e-18Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 0.00Glycolate oxidaseGLYCTO2 0.00TransketolaseTKT1 -0.0941NAD(P) transhydrogenase (periplasm)THD2pp 5.8322Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.158Polyphosphate kinasePPKr -1.00e+3Alcohol dehydrogenase (ethanol)ALCD2x -14.7Succinate transport via diffusion (extracellular to periplasm)SUCCtex -0.158Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 -0.0662Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 0.0033Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 18.5Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 0.00Succinate dehydrogenase (irreversible)SUCDi 0.00Formate transport via diffusion (cytoplasm to periplasm)FORtppi 31.6TransaldolaseTALA -3.58TransketolaseTKT2 -0.276D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 0.00Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 0.00Malate oxidaseMOX -0.00119CO2 transporter via diffusion (periplasm)CO2tpp 0.174Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 0.00Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA 0.00Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD -14.7HCO3 equilibration reactionHCO3E 0.250Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 13.0Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 18.5L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
### Growth on alternate substrates
Just as FBA was used to calculate growth rates of E. coli on glucose, it can also be used to simulate growth on other substrates. The iJO1366 computational model contains exchange reactions for 324 different compounds, 285 of these compounds contain at least one carbon atom. It is therefore possible to use iJO1366 to predict the growth capabilities of E. coli on a very wide range of media conditions.
As an example, we will simulate growth on succinate instead of glucose.

Growth on alternate substrates

Just as FBA was used to calculate growth rates of E. coli on glucose, it can also be used to simulate growth on other substrates. The iJO1366 computational model contains exchange reactions for 324 different compounds, 285 of these compounds contain at least one carbon atom. It is therefore possible to use iJO1366 to predict the growth capabilities of E. coli on a very wide range of media conditions.

As an example, we will simulate growth on succinate instead of glucose.

 
List all the exchange reactions. Iterate over the reactions and search for the string 'EX' in the reaction id (use `re.search` for string comparison). If the reaction id indicates an exchange reaction, print out the reaction name and id. Print also the total number of exchange reactions.

List all the exchange reactions. Iterate over the reactions and search for the string 'EX' in the reaction id (use re.search for string comparison). If the reaction id indicates an exchange reaction, print out the reaction name and id. Print also the total number of exchange reactions.

In [30]:
 
i = 0
for reac in model.reactions:
    if re.search(r'^EX', reac.id):
        print(reac.name, ', id:', reac.id)
        i += 1
        
print('Nb of exchange reactions: ',i)
(R)-Propane-1,2-diol exchange , id: EX_12ppd__R_e
(S)-Propane-1,2-diol exchange , id: EX_12ppd__S_e
1,4-alpha-D-glucan exchange , id: EX_14glucan_e
1,5-Diaminopentane exchange , id: EX_15dap_e
2',3'-Cyclic AMP exchange , id: EX_23camp_e
2',3'-Cyclic CMP exchange , id: EX_23ccmp_e
2',3'-Cyclic GMP exchange , id: EX_23cgmp_e
2',3'-Cyclic UMP exchange , id: EX_23cump_e
2,3-diaminopropionate exchange , id: EX_23dappa_e
Meso-2,6-Diaminoheptanedioate exchange , id: EX_26dap__M_e
2-Dehydro-3-deoxy-D-gluconate exchange , id: EX_2ddglcn_e
3,4-Dihydroxyphenylacetaldehyde exchange , id: EX_34dhpac_e
3'-AMP exchange , id: EX_3amp_e
3'-cmp exchange , id: EX_3cmp_e
3'-GMP exchange , id: EX_3gmp_e
3-hydroxycinnamic acid exchange , id: EX_3hcinnm_e
3-Hydroxypropanoate exchange , id: EX_3hpp_e
3-(3-hydroxy-phenyl)propionate exchange , id: EX_3hpppn_e
3'-UMP exchange , id: EX_3ump_e
4-Aminobutanoate exchange , id: EX_4abut_e
4-Hydroxyphenylacetaldehyde exchange , id: EX_4hoxpacd_e
5-Dehydro-D-gluconate exchange , id: EX_5dglcn_e
5-Methylthio-D-ribose exchange , id: EX_5mtr_e
L-alanine-D-glutamate exchange , id: EX_LalaDglu_e
L-alanine-D-glutamate-meso-2,6-diaminoheptanedioate exchange , id: EX_LalaDgluMdap_e
L-alanine-D-glutamate-meso-2,6-diaminoheptanedioate-D-alanine exchange , id: EX_LalaDgluMdapDala_e
L-alanine-L-glutamate exchange , id: EX_LalaLglu_e
Acetate exchange , id: EX_ac_e
Acetoacetate exchange , id: EX_acac_e
Acetaldehyde exchange , id: EX_acald_e
N-Acetyl-D-galactosamine exchange , id: EX_acgal_e
N-Acetyl-D-galactosamine 1-phosphate exchange , id: EX_acgal1p_e
N-Acetyl-D-glucosamine exchange , id: EX_acgam_e
N-Acetyl-D-glucosamine 1-phosphate exchange , id: EX_acgam1p_e
N-Acetyl-D-mannosamine exchange , id: EX_acmana_e
N-Acetylmuramate exchange , id: EX_acmum_e
N-Acetylneuraminate exchange , id: EX_acnam_e
4-Amino-4-deoxy-L-arabinose modified core oligosaccharide lipid A exchange , id: EX_acolipa_e
O-Acetyl-L-serine exchange , id: EX_acser_e
Adenine exchange , id: EX_ade_e
Adenosine exchange , id: EX_adn_e
Adenosylcobalamin exchange , id: EX_adocbl_e
Silver exchange , id: EX_ag_e
Agmatine exchange , id: EX_agm_e
2-Oxoglutarate exchange , id: EX_akg_e
Beta-Alanine exchange , id: EX_ala_B_e
D-Alanine exchange , id: EX_ala__D_e
L-Alanine exchange , id: EX_ala__L_e
D-Alanyl-D-alanine exchange , id: EX_alaala_e
D-Allose exchange , id: EX_all__D_e
Allantoin exchange , id: EX_alltn_e
AMP exchange , id: EX_amp_e
N-Acetyl-D-glucosamine(anhydrous)N-Acetylmuramic acid exchange , id: EX_anhgm_e
L-Arabinose exchange , id: EX_arab__L_e
Arbutin exchange , id: EX_arbt_e
Aerobactin minus Fe3 exchange , id: EX_arbtn_e
Aerobactin exchange , id: EX_arbtn_fe3_e
L-Arginine exchange , id: EX_arg__L_e
L-Ascorbate exchange , id: EX_ascb__L_e
L-Asparagine exchange , id: EX_asn__L_e
Arsenite exchange , id: EX_aso3_e
L-Aspartate exchange , id: EX_asp__L_e
Biotin exchange , id: EX_btn_e
Butyrate (n-C4:0) exchange , id: EX_but_e
Butanesulfonate exchange , id: EX_butso3_e
Calcium exchange , id: EX_ca2_e
Cobinamide exchange , id: EX_cbi_e
Cob(I)alamin exchange , id: EX_cbl1_e
Cadmium exchange , id: EX_cd2_e
Cys-Gly exchange , id: EX_cgly_e
Choline exchange , id: EX_chol_e
Chitobiose exchange , id: EX_chtbs_e
Citrate exchange , id: EX_cit_e
Chloride exchange , id: EX_cl_e
Chloramphenicol exchange , id: EX_cm_e
CMP exchange , id: EX_cmp_e
CO2 exchange , id: EX_co2_e
Co2+ exchange , id: EX_cobalt2_e
Core oligosaccharide lipid A exchange , id: EX_colipa_e
Core oligosaccharide lipid A diphosphate exchange , id: EX_colipap_e
Coprogen exchange , id: EX_cpgn_e
Coprogen unloaded (no Fe(III)) exchange , id: EX_cpgn_un_e
L-Carnitine exchange , id: EX_crn_e
D-carnitine exchange , id: EX_crn__D_e
Cytosine exchange , id: EX_csn_e
Cu+ exchange , id: EX_cu_e
Cu2+ exchange , id: EX_cu2_e
Hydrogen cyanide exchange , id: EX_cyan_e
Cyanate exchange , id: EX_cynt_e
D-Cysteine exchange , id: EX_cys__D_e
L-Cysteine exchange , id: EX_cys__L_e
Cytidine exchange , id: EX_cytd_e
Deoxyadenosine exchange , id: EX_dad_2_e
DAMP exchange , id: EX_damp_e
Decanoate (n-C10:0) exchange , id: EX_dca_e
DCMP exchange , id: EX_dcmp_e
Deoxycytidine exchange , id: EX_dcyt_e
Dodecanoate (n-C12:0) exchange , id: EX_ddca_e
DGMP exchange , id: EX_dgmp_e
Deoxyguanosine exchange , id: EX_dgsn_e
Dihydroxyacetone exchange , id: EX_dha_e
DIMP exchange , id: EX_dimp_e
Deoxyinosine exchange , id: EX_din_e
Dimethyl sulfide exchange , id: EX_dms_e
Dimethyl sulfoxide exchange , id: EX_dmso_e
Dopamine exchange , id: EX_dopa_e
Doxorubicin exchange , id: EX_doxrbcn_e
DTMP exchange , id: EX_dtmp_e
DUMP exchange , id: EX_dump_e
Deoxyuridine exchange , id: EX_duri_e
(enterobacterial common antigen)x4 core oligosaccharide lipid A exchange , id: EX_eca4colipa_e
Phosphoethanolamine KDO(2)-lipid (A) exchange , id: EX_enlipa_e
Enterochelin exchange , id: EX_enter_e
Ethanolamine exchange , id: EX_etha_e
Ethanesulfonate exchange , id: EX_ethso3_e
Ethanol exchange , id: EX_etoh_e
D-fructose 6-phosphate exchange , id: EX_f6p_e
Formaldehyde exchange , id: EX_fald_e
Fe2+ exchange , id: EX_fe2_e
Fe3+ exchange , id: EX_fe3_e
Fe(III)dicitrate exchange , id: EX_fe3dcit_e
Ferric 2,3-dihydroxybenzoylserine exchange , id: EX_fe3dhbzs_e
Fe(III)hydroxamate exchange , id: EX_fe3hox_e
Fe(III)hydoxamate, unloaded exchange , id: EX_fe3hox_un_e
Ferrichrome exchange , id: EX_fecrm_e
Ferrichrome minus Fe(III) exchange , id: EX_fecrm_un_e
Fe-enterobactin exchange , id: EX_feenter_e
Ferroxamine exchange , id: EX_feoxam_e
Ferroxamine minus Fe(3) exchange , id: EX_feoxam_un_e
Formate exchange , id: EX_for_e
D-Fructose exchange , id: EX_fru_e
Fructoselysine exchange , id: EX_frulys_e
D-Fructuronate exchange , id: EX_fruur_e
L-Fucose exchange , id: EX_fuc__L_e
Fumarate exchange , id: EX_fum_e
Fusidic acid exchange , id: EX_fusa_e
D-Glucose 1-phosphate exchange , id: EX_g1p_e
Sn-Glycero-3-phosphocholine exchange , id: EX_g3pc_e
Sn-Glycero-3-phosphoethanolamine exchange , id: EX_g3pe_e
Glycerophosphoglycerol exchange , id: EX_g3pg_e
Sn-Glycero-3-phospho-1-inositol exchange , id: EX_g3pi_e
Glycerophosphoserine exchange , id: EX_g3ps_e
D-Glucose 6-phosphate exchange , id: EX_g6p_e
D-Galactose exchange , id: EX_gal_e
Beta D-Galactose exchange , id: EX_gal_bD_e
Alpha-D-Galactose 1-phosphate exchange , id: EX_gal1p_e
D-Galactarate exchange , id: EX_galct__D_e
D-Galactonate exchange , id: EX_galctn__D_e
L-Galactonate exchange , id: EX_galctn__L_e
Galactitol exchange , id: EX_galt_e
D-Galacturonate exchange , id: EX_galur_e
D-Glucosamine exchange , id: EX_gam_e
D-Glucosamine 6-phosphate exchange , id: EX_gam6p_e
Gamma-butyrobetaine exchange , id: EX_gbbtn_e
GDP exchange , id: EX_gdp_e
D-Glucose exchange , id: EX_glc__D_e
D-Gluconate exchange , id: EX_glcn_e
D-Glucarate exchange , id: EX_glcr_e
D-Glucuronate exchange , id: EX_glcur_e
D-Glucuronate 1-phosphate exchange , id: EX_glcur1p_e
L-Glutamine exchange , id: EX_gln__L_e
L-Glutamate exchange , id: EX_glu__L_e
Glycine exchange , id: EX_gly_e
D-Glyceraldehyde exchange , id: EX_glyald_e
Glycine betaine exchange , id: EX_glyb_e
Glycerol exchange , id: EX_glyc_e
(R)-Glycerate exchange , id: EX_glyc__R_e
Glycerol 2-phosphate exchange , id: EX_glyc2p_e
Glycerol 3-phosphate exchange , id: EX_glyc3p_e
Glycolate exchange , id: EX_glyclt_e
GMP exchange , id: EX_gmp_e
Guanosine exchange , id: EX_gsn_e
Oxidized glutathione exchange , id: EX_gthox_e
Reduced glutathione exchange , id: EX_gthrd_e
GTP exchange , id: EX_gtp_e
Guanine exchange , id: EX_gua_e
H+ exchange , id: EX_h_e
H2 exchange , id: EX_h2_e
H2O exchange , id: EX_h2o_e
Hydrogen peroxide exchange , id: EX_h2o2_e
Hydrogen sulfide exchange , id: EX_h2s_e
Hepta-acylated core oligosaccharide lipid A (E. coli) exchange , id: EX_hacolipa_e
Hepta-acylated KDO(2)-lipid (A) exchange , id: EX_halipa_e
Hexadecanoate (n-C16:0) exchange , id: EX_hdca_e
Hexadecenoate (n-C16:1) exchange , id: EX_hdcea_e
Hg2+ exchange , id: EX_hg2_e
L-Histidine exchange , id: EX_his__L_e
L-Homoserine exchange , id: EX_hom__L_e
Hexanoate (n-C6:0) exchange , id: EX_hxa_e
Hypoxanthine exchange , id: EX_hxan_e
L-Idonate exchange , id: EX_idon__L_e
L-Isoleucine exchange , id: EX_ile__L_e
IMP exchange , id: EX_imp_e
Indole exchange , id: EX_indole_e
Myo-Inositol exchange , id: EX_inost_e
Inosine exchange , id: EX_ins_e
Isethionic acid exchange , id: EX_isetac_e
K+ exchange , id: EX_k_e
KDO(2)-lipid IV(A) exchange , id: EX_kdo2lipid4_e
D-lactate exchange , id: EX_lac__D_e
L-Lactate exchange , id: EX_lac__L_e
Lactose exchange , id: EX_lcts_e
L-Leucine exchange , id: EX_leu__L_e
KDO(2)-lipid (A) exchange , id: EX_lipa_e
Cold adapted KDO(2)-lipid (A) exchange , id: EX_lipa_cold_e
Lipoate exchange , id: EX_lipoate_e
L-Lysine exchange , id: EX_lys__L_e
L-Lyxose exchange , id: EX_lyx__L_e
D-Malate exchange , id: EX_mal__D_e
L-Malate exchange , id: EX_mal__L_e
Maltose exchange , id: EX_malt_e
Maltohexaose exchange , id: EX_malthx_e
Maltopentaose exchange , id: EX_maltpt_e
Maltotriose exchange , id: EX_malttr_e
Maltotetraose exchange , id: EX_maltttr_e
D-Mannose exchange , id: EX_man_e
D-Mannose 6-phosphate exchange , id: EX_man6p_e
2(alpha-D-Mannosyl)-D-glycerate exchange , id: EX_manglyc_e
Melibiose exchange , id: EX_melib_e
Methanol exchange , id: EX_meoh_e
D-Methionine exchange , id: EX_met__D_e
L-Methionine exchange , id: EX_met__L_e
L-methionine-R-sulfoxide exchange , id: EX_metsox_R__L_e
L-Methionine S-oxide exchange , id: EX_metsox_S__L_e
Mg exchange , id: EX_mg2_e
Minocycline exchange , id: EX_mincyc_e
Myo-Inositol hexakisphosphate exchange , id: EX_minohp_e
S-Methyl-L-methionine exchange , id: EX_mmet_e
Mn2+ exchange , id: EX_mn2_e
D-Mannitol exchange , id: EX_mnl_e
Molybdate exchange , id: EX_mobd_e
Methanesulfonate exchange , id: EX_mso3_e
Nitrous oxide exchange , id: EX_n2o_e
Sodium exchange , id: EX_na1_e
Nicotinate exchange , id: EX_nac_e
Ammonia exchange , id: EX_nh4_e
Ni2+ exchange , id: EX_ni2_e
NMN exchange , id: EX_nmn_e
Nitric oxide exchange , id: EX_no_e
Nitrite exchange , id: EX_no2_e
Nitrate exchange , id: EX_no3_e
Novobiocin exchange , id: EX_novbcn_e
(O16 antigen)x4 core oligosaccharide lipid A exchange , id: EX_o16a4colipa_e
O2 exchange , id: EX_o2_e
Superoxide anion exchange , id: EX_o2s_e
Octadecanoate (n-C18:0) exchange , id: EX_ocdca_e
Octadecenoate (n-C18:1) exchange , id: EX_ocdcea_e
Octanoate (n-C8:0) exchange , id: EX_octa_e
Ornithine exchange , id: EX_orn_e
Orotate exchange , id: EX_orot_e
Phenylacetaldehyde exchange , id: EX_pacald_e
Phenethylamine exchange , id: EX_peamn_e
L-Phenylalanine exchange , id: EX_phe__L_e
Protoheme exchange , id: EX_pheme_e
Phosphate exchange , id: EX_pi_e
(R)-Pantothenate exchange , id: EX_pnto__R_e
Propionate exchange , id: EX_ppa_e
Propanal exchange , id: EX_ppal_e
Phenylpropanoate exchange , id: EX_pppn_e
Phosphonate exchange , id: EX_ppt_e
L-Proline exchange , id: EX_pro__L_e
L-Prolinylglycine exchange , id: EX_progly_e
Psicoselysine exchange , id: EX_psclys_e
O-Phospho-L-serine exchange , id: EX_pser__L_e
Putrescine exchange , id: EX_ptrc_e
Pyridoxamine exchange , id: EX_pydam_e
Pyridoxal exchange , id: EX_pydx_e
Pyridoxine exchange , id: EX_pydxn_e
Pyruvate exchange , id: EX_pyr_e
Quinate exchange , id: EX_quin_e
Alpha-D-Ribose 5-phosphate exchange , id: EX_r5p_e
Rifampin exchange , id: EX_rfamp_e
D-Ribose exchange , id: EX_rib__D_e
L-Rhamnose exchange , id: EX_rmn_e
D-Sorbitol exchange , id: EX_sbt__D_e
Selenate exchange , id: EX_sel_e
D-Serine exchange , id: EX_ser__D_e
L-Serine exchange , id: EX_ser__L_e
Shikimate exchange , id: EX_skm_e
Selenite exchange , id: EX_slnt_e
Sulfur dioxide exchange , id: EX_so2_e
Sulfite exchange , id: EX_so3_e
Sulfate exchange , id: EX_so4_e
Spermidine exchange , id: EX_spmd_e
Succinate exchange , id: EX_succ_e
Sucrose exchange , id: EX_sucr_e
Sulfoacetate exchange , id: EX_sulfac_e
D-tartrate exchange , id: EX_tartr__D_e
L-tartrate exchange , id: EX_tartr__L_e
Taurine exchange , id: EX_taur_e
Thiocyanate exchange , id: EX_tcynt_e
Thiamin exchange , id: EX_thm_e
L-Threonine exchange , id: EX_thr__L_e
L-Threonine O-3-phosphate exchange , id: EX_thrp_e
Thymine exchange , id: EX_thym_e
Thymidine exchange , id: EX_thymd_e
Trimethylamine exchange , id: EX_tma_e
Trimethylamine N-oxide exchange , id: EX_tmao_e
Trehalose exchange , id: EX_tre_e
L-Tryptophan exchange , id: EX_trp__L_e
Thiosulfate exchange , id: EX_tsul_e
Tetradecanoate (n-C14:0) exchange , id: EX_ttdca_e
Tetradecenoate (n-C14:1) exchange , id: EX_ttdcea_e
Tetracycline exchange , id: EX_ttrcyc_e
Tungstate exchange , id: EX_tungs_e
Tyramine exchange , id: EX_tym_e
L-Tyrosine exchange , id: EX_tyr__L_e
Phosphotyrosine exchange , id: EX_tyrp_e
UDP-N-acetyl-D-glucosamine exchange , id: EX_uacgam_e
UDP-N-acetyl-D-galactosamine exchange , id: EX_udpacgal_e
UDPglucose exchange , id: EX_udpg_e
UDPgalactose exchange , id: EX_udpgal_e
UDP-D-glucuronate exchange , id: EX_udpglcur_e
UMP exchange , id: EX_ump_e
Uracil exchange , id: EX_ura_e
Urea exchange , id: EX_urea_e
Uridine exchange , id: EX_uri_e
L-Valine exchange , id: EX_val__L_e
Xanthine exchange , id: EX_xan_e
Xanthosine 5'-phosphate exchange , id: EX_xmp_e
Xanthosine exchange , id: EX_xtsn_e
D-Xylose exchange , id: EX_xyl__D_e
L-Xylulose exchange , id: EX_xylu__L_e
Zinc exchange , id: EX_zn2_e
Nb of exchange reactions:  324
 
#### Aerobic growth on succinate

Aerobic growth on succinate

 
Search for the succinate exchange reaction id in the list of reactions. Iterate over the reactions and use string comparison `re.search` to search for the reaction name.

Search for the succinate exchange reaction id in the list of reactions. Iterate over the reactions and use string comparison re.search to search for the reaction name.

In [31]:
 
for reac in model.reactions:
    if re.search(r'succinate', reac.name, re.I) and re.search(r'exchange', reac.name, re.I):
        print(reac.name, ', id:', reac.id)
Succinate exchange , id: EX_succ_e
 
Set the following conditions: aerobic growth (illimited o2 uptake), no glucose and succinate (maximum uptake rate: 20). Then, compute the growth rate and plot the fluxes on the metabolic map.

Set the following conditions: aerobic growth (illimited o2 uptake), no glucose and succinate (maximum uptake rate: 20). Then, compute the growth rate and plot the fluxes on the metabolic map.

In [32]:
 
# aerobic conditions
o2_exchange.lower_bound = -1000
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
# No glucose
glc_exchange.lower_bound = 0
print(glc_exchange.lower_bound, "< EX_glc__D_e <", glc_exchange.upper_bound)
# Succinate uptake
succ_exchange = model.reactions.get_by_id('EX_succ_e')
succ_exchange.lower_bound = -20
print(succ_exchange.lower_bound, "< EX_succ_e <", succ_exchange.upper_bound)
solution = model.optimize()
print('Growth rate: %.2f' % solution.f)
# Set back to default values
succ_exchange.lower_bound = 0
glc_exchange.lower_bound = -18.5
metabolicMap.reaction_data=solution.x_dict
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
-1000 < EX_o2_e < 1000.0
0 < EX_glc__D_e < 1000.0
-20 < EX_succ_e < 1000.0
Growth rate: 1.00
Out[32]:
Malate dehydrogenaseMDH 13.9Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp 0.0033NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 0.00Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 0.00Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 0.00Ethanol reversible transport via diffusion (periplasm)ETOHtrpp 0.00Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 28.5DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 5.99Glucose-1-phosphate adenylyltransferaseGLGC 0.00Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 0.00Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK 2.40Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex 0.00Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 0.00Glucose 6-phosphate dehydrogenaseG6PDH2r 0.00Acetyl-CoA synthetaseACS 997Glycerol kinaseGLYK 0.002-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 0.00(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp 72.543NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 0.00Acetate kinaseACKr -996Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI -0.735D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 53.80.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 0.00Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx 0.00Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 0.00CO2 transport via diffusion (extracellular to periplasm)CO2tex -39.0Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 4.95L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 9.15Malic enzyme (NADP)ME2 12.1Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 28.5Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp 0.00Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 5.99Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 26.02-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 0.00Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 0.00Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM 4.12Ribulose 5-phosphate 3-epimeraseRPE -0.775Fumarate reductaseFRD2 0.00NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 0.001,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 20.0Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.869Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI -1.01(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 0.00Isocitrate dehydrogenase (NADP)ICDHyr 5.99D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex 0.00EnolaseENO -4.12L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 996Glyceraldehyde-3-phosphate dehydrogenaseGAPD -2.40Citrate transport out via proton antiport (periplasm)CITt3pp 0.00Succinyl-CoA synthetase (ADP-forming)SUCOAS -4.39Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 5.99PhosphofructokinasePFK 0.00D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex 0.00ATP maintenance requirementATPM 3.15Phosphofructokinase (s7p)PFK_3 0.00Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.00Fructose 6-phosphate aldolaseF6PA 0.00Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp 0.00Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 0.00Glycolate oxidaseGLYCTO2 0.000668TransketolaseTKT1 -0.197NAD(P) transhydrogenase (periplasm)THD2pp 0.0022Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.00Polyphosphate kinasePPKr -1.00e+3Alcohol dehydrogenase (ethanol)ALCD2x 0.00Succinate transport via diffusion (extracellular to periplasm)SUCCtex 20.0Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 -0.139Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 0.0033Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 0.00Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 0.00Succinate dehydrogenase (irreversible)SUCDi 53.4Formate transport via diffusion (cytoplasm to periplasm)FORtppi 0.00TransaldolaseTALA -0.197TransketolaseTKT2 -0.578D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 4.92Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 0.00Malate oxidaseMOX 0.00162CO2 transporter via diffusion (periplasm)CO2tpp -39.0Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 0.00Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA -0.869Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD 4.85HCO3 equilibration reactionHCO3E 0.525Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 0.00Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
#### Anaerobic growth on succinate

Anaerobic growth on succinate

 
Similarly, we compute the growth rate on succinate under anaerobic conditions.
First, we set the maximum o2 uptake rate to 0.

Similarly, we compute the growth rate on succinate under anaerobic conditions.

First, we set the maximum o2 uptake rate to 0.

In [33]:
 
# anaerobic conditions
o2_exchange.lower_bound = 0
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
# No glucose
glc_exchange.lower_bound = 0
# Succinate uptake
succ_exchange.lower_bound = -20
0 < EX_o2_e < 1000.0
 
Then, we compute the optimal solution and print the status from the solver.

Then, we compute the optimal solution and print the status from the solver.

In [34]:
 
solution = model.optimize()
print('Satus: ',solution.status)
# Set back to default values
succ_exchange.lower_bound = 0
glc_exchange.lower_bound = -18.5
Satus:  infeasible
 
In this case, the optimal solution does not exists and the linear programming solver of the COBRA package returns the status "infeasible". FBA predicts that growth is not possible on succinate under anaerobic conditions, because the maximum amount of ATP that can be produced from this amount of succinate is less than the minimum bound  of the non-growth associated maintenance (NGAM) reaction.
Growth-associated maintenance (GAM) and non-growth-associated maintenance (NGAM) are the amounts of ATP consumed during cell growth and by non-growth associated processes such as maintenance of membrane gradients, respectively. GAM is a component of the biomass reaction, while NGAM is manifest as a lower bound on the separate ATP draining reaction “ATPM.”
<img src="Images/Thiele2010_growth_associated_maintenance_plot.png" width="400" />
_Thiele, I., & Palsson, B. Ø. (2010). A protocol for generating a high-quality genome-scale metabolic reconstruction. Nature Protocols, 5(1), 93–121._
Print the lower bound of the ATPM reaction in the iJO1366 model, reaction id `ATPM`.

In this case, the optimal solution does not exists and the linear programming solver of the COBRA package returns the status "infeasible". FBA predicts that growth is not possible on succinate under anaerobic conditions, because the maximum amount of ATP that can be produced from this amount of succinate is less than the minimum bound of the non-growth associated maintenance (NGAM) reaction.

Growth-associated maintenance (GAM) and non-growth-associated maintenance (NGAM) are the amounts of ATP consumed during cell growth and by non-growth associated processes such as maintenance of membrane gradients, respectively. GAM is a component of the biomass reaction, while NGAM is manifest as a lower bound on the separate ATP draining reaction “ATPM.”

Thiele, I., & Palsson, B. Ø. (2010). A protocol for generating a high-quality genome-scale metabolic reconstruction. Nature Protocols, 5(1), 93–121.

Print the lower bound of the ATPM reaction in the iJO1366 model, reaction id ATPM.

In [35]:
 
model.reactions.ATPM.lower_bound
Out[35]:
3.15
 
The minimum amount of ATP molecules consumed for non-growth maintenance is 3.15 mmol gDW<sup>-1</sup> h<sup>-1</sup>.

The minimum amount of ATP molecules consumed for non-growth maintenance is 3.15 mmol gDW-1 h-1.

 
#### Growth on pyruvate

Growth on pyruvate

 
Repeat the same steps to compute the growth rate under aerobic and anaerobic conditions on pyruvate.
Hint: to search for the pyruvate exchange reaction, use IPython list tab completion on the `model.reactions` object, knowing that all exchange reactions start with "EX_".

Repeat the same steps to compute the growth rate under aerobic and anaerobic conditions on pyruvate.

Hint: to search for the pyruvate exchange reaction, use IPython list tab completion on the model.reactions object, knowing that all exchange reactions start with "EX_".

In [36]:
 
# aerobic conditions
o2_exchange.lower_bound = -1000
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
# No glucose
glc_exchange.lower_bound = 0
print(glc_exchange.lower_bound, "< EX_glc__D_e <", glc_exchange.upper_bound)
# Pyruvate uptake
pyruvate_exchange = model.reactions.EX_pyr_e
pyruvate_exchange.lower_bound = -20
print(pyruvate_exchange.lower_bound, "< EX_pyr_e <", pyruvate_exchange.upper_bound)
solution = model.optimize()
print('Growth rate: %.2f' % solution.f)
metabolicMap.reaction_data=solution.x_dict
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
-1000 < EX_o2_e < 1000.0
0 < EX_glc__D_e < 1000.0
-20 < EX_pyr_e < 1000.0
Growth rate: 0.73
Out[36]:
Malate dehydrogenaseMDH 11.9Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp 0.0033NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 0.00Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 2.17Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 0.00Ethanol reversible transport via diffusion (periplasm)ETOHtrpp 0.00Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 0.00DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 9.77Glucose-1-phosphate adenylyltransferaseGLGC 0.00Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 0.00Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK 1.76Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex 0.00Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 0.00Glucose 6-phosphate dehydrogenaseG6PDH2r 0.00Acetyl-CoA synthetaseACS 997Glycerol kinaseGLYK 0.002-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 0.00(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp 54.443NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 27.5Acetate kinaseACKr -997Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI -0.539D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 36.80.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 0.00Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx 0.00Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 0.00CO2 transport via diffusion (extracellular to periplasm)CO2tex -29.9Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 0.00L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 14.2Malic enzyme (NADP)ME2 0.00Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 0.00Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp 0.00Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 9.77Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 9.752-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 0.0800Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 0.00Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM 2.98Ribulose 5-phosphate 3-epimeraseRPE -0.568Fumarate reductaseFRD2 0.00NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 3.591,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 0.00Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.637Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI -0.741(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 2.17Isocitrate dehydrogenase (NADP)ICDHyr 7.60D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex 0.00EnolaseENO -2.98L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 997Glyceraldehyde-3-phosphate dehydrogenaseGAPD -1.76Citrate transport out via proton antiport (periplasm)CITt3pp 0.00Succinyl-CoA synthetase (ADP-forming)SUCOAS -6.43Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 9.77PhosphofructokinasePFK 0.00D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex 0.00ATP maintenance requirementATPM 3.15Phosphofructokinase (s7p)PFK_3 0.00Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.00Fructose 6-phosphate aldolaseF6PA 0.00Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp 0.00Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 20.0Glycolate oxidaseGLYCTO2 0.000490TransketolaseTKT1 -0.144NAD(P) transhydrogenase (periplasm)THD2pp 2.1422Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.00Polyphosphate kinasePPKr -1.00e+3Alcohol dehydrogenase (ethanol)ALCD2x 0.00Succinate transport via diffusion (extracellular to periplasm)SUCCtex 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 -0.102Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 0.0033Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 0.00Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 20.0Succinate dehydrogenase (irreversible)SUCDi 9.22Formate transport via diffusion (cytoplasm to periplasm)FORtppi 0.00TransaldolaseTALA -0.144TransketolaseTKT2 -0.424D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 6.82Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 0.00Malate oxidaseMOX 0.00119CO2 transporter via diffusion (periplasm)CO2tpp -29.9Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 0.00Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA -0.637Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD 4.55e-13HCO3 equilibration reactionHCO3E 0.385Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 0.00Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
In [37]:
 
# anaerobic conditions
o2_exchange.lower_bound = 0
print(o2_exchange.lower_bound, "< EX_o2_e <", o2_exchange.upper_bound)
# No glucose
glc_exchange.lower_bound = 0
# Pyruvate uptake
pyruvate_exchange.lower_bound = -20
solution = model.optimize()
print('Growth rate: %.2f' % solution.f)
# Set back to default values
glc_exchange.lower_bound = -18.5
succ_exchange.lower_bound = 0
pyruvate_exchange.lower_bound = 0
metabolicMap.reaction_data=solution.x_dict
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
0 < EX_o2_e < 1000.0
Growth rate: 0.11
Out[37]:
Malate dehydrogenaseMDH 0.0817Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp -1.33e-1833NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 0.377Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 0.00Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 0.00Ethanol reversible transport via diffusion (periplasm)ETOHtrpp 0.00Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 0.00DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 0.123Glucose-1-phosphate adenylyltransferaseGLGC 0.00Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 0.00Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK 0.276Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex 0.00Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 0.00Glucose 6-phosphate dehydrogenaseG6PDH2r 0.00Acetyl-CoA synthetaseACS 0.00Glycerol kinaseGLYK 0.002-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 0.00(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp -5.2543NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 0.00Acetate kinaseACKr -18.2Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI -0.0843D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 0.000.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 0.00Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx -5.63e-19Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 0.00CO2 transport via diffusion (extracellular to periplasm)CO2tex -1.78Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 0.00L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 1.82Malic enzyme (NADP)ME2 0.00Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 0.00Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp -18.2Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 0.123Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 0.08142-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 16.9Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 0.00Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM 0.466Ribulose 5-phosphate 3-epimeraseRPE -0.0889Fumarate reductaseFRD2 -3.92e-19NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 0.9381,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 0.00Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.0997Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI -0.116(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 0.00Isocitrate dehydrogenase (NADP)ICDHyr 0.123D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex -16.9EnolaseENO -0.466L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 18.2Glyceraldehyde-3-phosphate dehydrogenaseGAPD -0.276Citrate transport out via proton antiport (periplasm)CITt3pp 0.0379Succinyl-CoA synthetase (ADP-forming)SUCOAS 0.0601Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 0.123PhosphofructokinasePFK 0.00D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex -18.2ATP maintenance requirementATPM 3.15Phosphofructokinase (s7p)PFK_3 0.00Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.0379Fructose 6-phosphate aldolaseF6PA 0.00Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp -1.10e-15Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 20.0Glycolate oxidaseGLYCTO2 0.00TransketolaseTKT1 -0.0226NAD(P) transhydrogenase (periplasm)THD2pp 1.4022Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.00Polyphosphate kinasePPKr -0.401Alcohol dehydrogenase (ethanol)ALCD2x 0.00Succinate transport via diffusion (extracellular to periplasm)SUCCtex -0.0379Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 -0.0159Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 4.31e-1933Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 0.00Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 20.0Succinate dehydrogenase (irreversible)SUCDi 0.00Formate transport via diffusion (cytoplasm to periplasm)FORtppi 16.9TransaldolaseTALA -0.0226TransketolaseTKT2 -0.0663D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 0.00Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 0.00Malate oxidaseMOX -0.000286CO2 transporter via diffusion (periplasm)CO2tpp -1.78Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 0.00Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA -0.0997Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD 0.00HCO3 equilibration reactionHCO3E 0.0602Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 0.00Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 0.00L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
### Simulating different objective function: maximize ATP production.
FBA can also be used to determine the maximum yields of important cofactors and biosynthetic precursors from glucose and other substrates.
In this example, we will compute the maximum yields of the cofactors ATP, NADH, and NADPH from glucose under aerobic conditions. To calculate the optimal ATP production, first constrain the glucose exchange reaction to exactly -1 mmol gDW<sup>-1</sup> h<sup>-1</sup> by setting both the lower and upper bounds to -1.

Simulating different objective function: maximize ATP production.

FBA can also be used to determine the maximum yields of important cofactors and biosynthetic precursors from glucose and other substrates.

In this example, we will compute the maximum yields of the cofactors ATP, NADH, and NADPH from glucose under aerobic conditions. To calculate the optimal ATP production, first constrain the glucose exchange reaction to exactly -1 mmol gDW-1 h-1 by setting both the lower and upper bounds to -1.

In [38]:
 
# aerobic conditions
o2_exchange.lower_bound = -1000
# No other carbon sources
succ_exchange.lower_bound = 0
pyruvate_exchange.lower_bound = 0
# Constrain glucose uptake
glc_exchange.lower_bound = -1
glc_exchange.upper_bound = -1
print(glc_exchange.lower_bound, "< EX_glc__D_e <", glc_exchange.upper_bound)
-1 < EX_glc__D_e < -1
 
We can check the maximum rate for all the uptake reactions by listing them. Iterate over the reactions and search for reaction that contain exchange in their name and with a non-zero lower bound. Print the reaction bounds, reaction name and id.

We can check the maximum rate for all the uptake reactions by listing them. Iterate over the reactions and search for reaction that contain exchange in their name and with a non-zero lower bound. Print the reaction bounds, reaction name and id.

In [39]:
 
# Print all the uptake reactions with non-zero lower bound
for reac in model.reactions:
    if re.search(r'exchange', reac.name, re.I) and reac.lower_bound < 0:
        print('{: 8.1f} < v < {: 8.1f}'.format(reac.lower_bound, reac.upper_bound),', ', reac.name, ', id:', reac.id)
 -1000.0 < v <   1000.0 ,  Calcium exchange , id: EX_ca2_e
    -0.0 < v <   1000.0 ,  Cob(I)alamin exchange , id: EX_cbl1_e
 -1000.0 < v <   1000.0 ,  Chloride exchange , id: EX_cl_e
 -1000.0 < v <   1000.0 ,  CO2 exchange , id: EX_co2_e
 -1000.0 < v <   1000.0 ,  Co2+ exchange , id: EX_cobalt2_e
 -1000.0 < v <   1000.0 ,  Cu2+ exchange , id: EX_cu2_e
 -1000.0 < v <   1000.0 ,  Fe2+ exchange , id: EX_fe2_e
 -1000.0 < v <   1000.0 ,  Fe3+ exchange , id: EX_fe3_e
    -1.0 < v <     -1.0 ,  D-Glucose exchange , id: EX_glc__D_e
 -1000.0 < v <   1000.0 ,  H+ exchange , id: EX_h_e
 -1000.0 < v <   1000.0 ,  H2O exchange , id: EX_h2o_e
 -1000.0 < v <   1000.0 ,  K+ exchange , id: EX_k_e
 -1000.0 < v <   1000.0 ,  Mg exchange , id: EX_mg2_e
 -1000.0 < v <   1000.0 ,  Mn2+ exchange , id: EX_mn2_e
 -1000.0 < v <   1000.0 ,  Molybdate exchange , id: EX_mobd_e
 -1000.0 < v <   1000.0 ,  Sodium exchange , id: EX_na1_e
 -1000.0 < v <   1000.0 ,  Ammonia exchange , id: EX_nh4_e
 -1000.0 < v <   1000.0 ,  Ni2+ exchange , id: EX_ni2_e
 -1000.0 < v <   1000.0 ,  O2 exchange , id: EX_o2_e
 -1000.0 < v <   1000.0 ,  Phosphate exchange , id: EX_pi_e
 -1000.0 < v <   1000.0 ,  Selenate exchange , id: EX_sel_e
 -1000.0 < v <   1000.0 ,  Selenite exchange , id: EX_slnt_e
 -1000.0 < v <   1000.0 ,  Sulfate exchange , id: EX_so4_e
 -1000.0 < v <   1000.0 ,  Tungstate exchange , id: EX_tungs_e
 -1000.0 < v <   1000.0 ,  Zinc exchange , id: EX_zn2_e
 
Next, set the ATP maintenance reaction (id `ATPM`) as the objective to be maximized using the `change_objective` function. ATPM is a stoichiometrically balanced reaction that hydrolyzes ATP (`atp_c`) and produces ADP (`adp_c`), inorganic phosphate (`pi_c`), and a proton (`h_c`). It works as an objective for maximizing ATP production because in order to consume the maximum amount of ATP, the network must first produce ATP by the most efficient pathways available by recharging the produced ADP.

Next, set the ATP maintenance reaction (id ATPM) as the objective to be maximized using the change_objective function. ATPM is a stoichiometrically balanced reaction that hydrolyzes ATP (atp_c) and produces ADP (adp_c), inorganic phosphate (pi_c), and a proton (h_c). It works as an objective for maximizing ATP production because in order to consume the maximum amount of ATP, the network must first produce ATP by the most efficient pathways available by recharging the produced ADP.

In [40]:
 
model.change_objective('ATPM')
model.reactions.ATPM.reaction
Out[40]:
'h2o_c + atp_c --> pi_c + adp_c + h_c'
 
As we have seen above (anaerobic growth on succinate), by default this reaction has a lower bound of 3.15 mmol gDW<sup>-1</sup> h<sup>-1</sup> to simulate non-growth associated maintenance costs. Remove the constraint on this reaction by setting the lower bounds to 0 and the upper bound to 1000.

As we have seen above (anaerobic growth on succinate), by default this reaction has a lower bound of 3.15 mmol gDW-1 h-1 to simulate non-growth associated maintenance costs. Remove the constraint on this reaction by setting the lower bounds to 0 and the upper bound to 1000.

In [41]:
 
model.reactions.ATPM.lower_bound = 0
model.reactions.ATPM.upper_bound = 1000
 
Calculate the optimal solution which should give the maximum yield of ATP. Now the optimal objective value is not the biomass production anymore, but rather the flux through the ATP production reaction in units of mmol gDW<sup>-1</sup> h<sup>-1</sup>. Because the uptake rate of glucose has been set to exactly -1 mmol gDW<sup>-1</sup> h<sup>-1</sup>, we can obtain easily the ratio of ATP molecules produced per glucose molecules consumed. The result should be 23.5 mol ATP/mol glucose.

Calculate the optimal solution which should give the maximum yield of ATP. Now the optimal objective value is not the biomass production anymore, but rather the flux through the ATP production reaction in units of mmol gDW-1 h-1. Because the uptake rate of glucose has been set to exactly -1 mmol gDW-1 h-1, we can obtain easily the ratio of ATP molecules produced per glucose molecules consumed. The result should be 23.5 mol ATP/mol glucose.

In [42]:
 
solution = model.optimize()
print('Maximum ATP production rate:', solution.f, 'mol ATP/mol glucose')
Maximum ATP production rate: 23.500000000014005 mol ATP/mol glucose
In [43]:
 
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              reaction_data=solution.x_dict,
                              # color and size according to the absolute value
                              reaction_styles=['color', 'size', 'abs', 'text'],
                              # change the default colors
                              reaction_scale=[{'type': 'min', 'color': '#cccccc', 'size': 4},
                                              {'type': 'mean', 'color': '#0000dd', 'size': 20},
                                              {'type': 'max', 'color': '#ff0000', 'size': 40}],
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
Out[43]:
Malate dehydrogenaseMDH 4.00Nitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp 0.0033NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4 0.00NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17pp 0.00L-malate transport out via proton antiport (periplasm)MALt3pp 0.00D-lactate transport via proton symport (periplasm)D_LACt2pp 0.00Glucose-1-phosphataseG1PPpp 0.00Trans-aconitate methyltransferaseACONMT 0.00Acetaldehyde transport via diffusion (extracellular to periplasm)ACALDtex 0.00Glycolate oxidaseGLYCTO3 0.00Aconitate isomerase (spontaneous)ACONIs 0.00Cytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp 0.000.5Phosphoenolpyruvate carboxylasePPC 0.00Fructose 6-phosphate transport via diffusion (extracellular to periplasm)F6Ptex 0.00Malate synthaseMALS 2.45e-13Hydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp 0.0022Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3 0.00Ethanol reversible transport via diffusion (periplasm)ETOHtrpp 0.00Cytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp 0.000.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2pp 0.00Glycogen phosphorylaseGLCP 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2bpp 0.00NADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18pp 0.00DsbA protein reoxidation reaction (aerobic)DSBAO1 0.00Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2pp 0.00Citrate synthaseCS 2.00Glucose-1-phosphate adenylyltransferaseGLGC 0.00Glycerol transport via channel (periplasm)GLYCtpp 0.00Glycolate oxidaseGLYCTO4 0.00Glucose-6-phosphate isomerasePGI 1.00Glycerol transport via diffusion (extracellular to periplasm)GLYCtex 0.00Quinol monooxygenase (menaquinol 8)QMO3 0.0022Hydroxyacylglutathione hydrolaseGLYOX 0.00Phosphoglycerate kinasePGK -2.00Fumarate transport via diffusion (extracellular to periplasm)FUMtex 0.00CatalaseCAT 0.0022Ethanol transport via diffusion (extracellular to periplasm)ETOHtex 0.00Hydrogen transport diffusion (periplasm)H2tpp 0.00Superoxide dismutaseSPODMpp 0.0022Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5 0.00PhosphoglucomutasePGMT 0.00Glucose 6-phosphate dehydrogenaseG6PDH2r 0.00Acetyl-CoA synthetaseACS 0.00Glycerol kinaseGLYK 0.002-oxoglutarate reversible transport via symport (periplasm)AKGt2rpp 0.00Malate transport via proton symport (2 H) (periplasm)MALt2_2pp 0.006-phosphogluconolactonasePGL 0.00(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtpp 0.00Dimethyl sulfoxide transport via diffusion (periplasm)DMSOtpp 0.00ATP synthase (four protons for one ATP) (periplasm)ATPS4rpp 19.543NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16pp 10.0Acetate kinaseACKr 0.00Glycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2 0.00Ribose-5-phosphate isomeraseRPI 4.55e-13D-xylose transport in via proton symport (periplasm)XYLt2pp 0.00D-glucose 1-phosphate transport via diffusionG1Ptex 0.00Malate transport via diffusion (extracellular to periplasm)MALtex 0.00Cytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp 12.00.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1pp 0.00D-fructose transport via PEP:Pyr PTS (periplasm)FRUptspp 0.00Polyphosphate kinasePPK2r 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00Pyruvate kinasePYK 5.68e-13Quinol monooxygenase (Ubiquinol-8)QMO2 0.00L-lactate reversible transport via proton symport (periplasm)L_LACt2rpp 0.00NADH dehydrogenase (menaquinone-8 & 0 protons)NADH10 0.00Glycerol dehydrogenaseGLYCDx 0.00Malate transport via proton symport (3 H) (periplasm)MALt2_3pp 0.00Dihydroxyacetone phosphotransferaseDHAPT 1.00CO2 transport via diffusion (extracellular to periplasm)CO2tex -6.00Nitrate reductase (Ubiquinol-8)NO3R1bpp 0.00DsbA protein reoxidation reaction (anaerobic)DSBAO2 0.00Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3Pabcpp 0.00Phosphoenolpyruvate carboxykinasePPCK 0.00L-lactate transport via diffusion (extracellular to periplasm)L_LACtex 0.00Pyruvate dehydrogenasePDH 2.00Malic enzyme (NADP)ME2 0.00Acetaldehyde reversible transport (periplasm)ACALDtpp 0.00D-fructose transport via diffusion (extracellular to periplasm)FRUtex 0.00D-xylose transport via ABC system (periplasm)XYLabcpp 0.00Fumarate reductaseFRD3 0.00Inorganic triphosphatasePPA2 0.00Acetate reversible transport via proton symport (periplasm)ACt2rpp 0.00Hydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp 0.0022Pyruvate oxidasePOX 0.00NADPH Quinone Reductase (Ubiquinone-8)NADPHQR2 0.00Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTb 2.00Citrate transport via diffusion (extracellular to periplasm)CITtex 0.00D-ribose transport via ABC system (periplasm)RIBabcpp 0.00FumaraseFUM 4.002-dehydro-3-deoxy-phosphogluconate aldolaseEDA 0.00Pyruvate formate lyasePFL 0.00Inorganic diphosphatasePPA 0.002Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1pp 0.00Glycogen phosphorylaseGLCP2 0.00Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1pp 0.00NADH dehydrogenase (ubiquinone-8 )NADH5 0.00D-lactate dehydrogenaseLDH_D 6.82e-13Lacaldehyde reductase (R-propane-1,2-diol forming)LCARR 0.00Phosphoglycerate mutasePGM -2.00Ribulose 5-phosphate 3-epimeraseRPE 0.00Fumarate reductaseFRD2 0.00NADPH Quinone Reductase (Menaquinone-8)NADPHQR3 0.00Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3Ptex 0.00Phosphoenolpyruvate synthasePPS 0.001,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2 0.00Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 1.00Trimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2 0.00Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5pp 0.00Superoxide dismutaseSPODM 0.0022Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2pp 0.00Succintate transport via proton symport (3 H) (periplasm)SUCCt2_3pp 0.00Fructose-bisphosphataseFBP 0.00Hydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp 0.0022Triose-phosphate isomeraseTPI 1.00(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtex 0.00Isocitrate lyaseICL 2.13e-13Isocitrate dehydrogenase (NADP)ICDHyr 2.00D-lactate transport via diffusion (extracellular to periplasm)D_LACtex 0.00Malate dehydrogenase (menaquinone 8 as acceptor)MDH3 0.00Formate transport via diffusion (extracellular to periplasm)FORtex 4.89e-12EnolaseENO 2.00L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00Glycerol-3-phosphataseG3PT 0.00Glucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDpp 0.00D-glucose transport in via proton symport (periplasm)GLCt2pp 0.00RibokinaseRBK 0.00PhosphotransacetylasePTAr 0.00Glyceraldehyde-3-phosphate dehydrogenaseGAPD 2.00Citrate transport out via proton antiport (periplasm)CITt3pp 0.00Succinyl-CoA synthetase (ADP-forming)SUCOAS -2.00Hydrogen transport via diffusion (extracellular to periplasm)H2tex 0.00Aconitase (half-reaction A, Citrate hydro-lyase)ACONTa 2.00PhosphofructokinasePFK 0.00D-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2x 0.00Acetate transport via diffusion (extracellular to periplasm)ACtex 0.00ATP maintenance requirementATPM 23.5Phosphofructokinase (s7p)PFK_3 0.00Methylglyoxal synthaseMGSA 0.00NADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9 0.00Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2pp 0.00Nitrite Reductase (NADH)NTRIR2x 0.00Citrate transport via succinate antiport (periplasm)CITt7pp 0.00Fructose 6-phosphate aldolaseF6PA 1.00Malate dehydrogenase (ubiquinone 8 as acceptor)MDH2 0.00Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6pp 0.00Pyruvate reversible transport via proton symport (periplasm)PYRt2rpp 0.00Glycolate oxidaseGLYCTO2 0.00TransketolaseTKT1 0.00NAD(P) transhydrogenase (periplasm)THD2pp 0.0022Succinate transport out via proton antiport (periplasm)SUCCt3pp 0.00Polyphosphate kinasePPKr 3.41e-13Alcohol dehydrogenase (ethanol)ALCD2x 0.00Succinate transport via diffusion (extracellular to periplasm)SUCCtex 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2 0.00Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2x 0.00Glycerol-3-phosphate dehydrogenase (NADP)G3PD2 0.00Xylose isomeraseXYLI1 0.00Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp 0.0033Citrate lyaseCITL 0.00Formate transport via proton symport (uptake only, periplasm)FORt2pp 0.00Glucose transport via diffusion (extracellular to periplasm)GLCtex_copy1 1.00Pyruvate transport via diffusion (extracellular to periplasm)PYRtex 0.00Succinate dehydrogenase (irreversible)SUCDi 2.00Formate transport via diffusion (cytoplasm to periplasm)FORtppi -2.27e-13TransaldolaseTALA 0.00TransketolaseTKT2 0.00D-xylose transport via diffusion (extracellular to periplasm)XYLtex 0.002-Oxogluterate dehydrogenaseAKGDH 2.00Alpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtex 0.00Nitrate reductase (Menaquinol-8) (periplasm)NO3R2pp 0.00Lactoylglutathione lyaseLGTHL 0.00Aldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y 0.006-phosphogluconate dehydrataseEDD 0.00Fructose-1-phosphate kinaseFRUK 0.00Formate dehydrogenase (quinone-8) (periplasm)FDH4pp 4.64e-12Malate oxidaseMOX 1.71e-12CO2 transporter via diffusion (periplasm)CO2tpp -6.00Malic enzyme (NAD)ME1 0.00XylulokinaseXYLK 0.00Glucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2pp 0.00NAD transhydrogenaseNADTRHD 0.00Glycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6 0.00Phosphogluconate dehydrogenaseGND 0.00Hexokinase (D-glucose:ATP)HEX1 0.00Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1 0.00Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3pp 0.00Trimethylamine N-oxide reductase (menaquinol 8)TMAOR1 0.00Fructose-bisphosphate aldolaseFBA 0.00Glucose-6-phosphate phosphataseG6PP 0.00Ribose transport via diffusion (extracellular to periplasm)RIBtex 0.00Fructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2pp 0.00Acetaldehyde dehydrogenase (acetylating)ACALD 0.00HCO3 equilibration reactionHCO3E 0.00Formate-hydrogen lyaseFHL 0.00Glycogen synthase (ADPGlc)GLCS1 0.00Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6Ptex 0.00Oxaloacetate decarboxylaseOAADC 0.00Dimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2pp 0.00D-lactate dehydrogenaseLDH_D2 0.00D-lactate dehydrogenaseLDH_D2 0.00L-Lactate dehydrogenase (ubiquinone)L_LACD2 0.00D-glucose transport via PEP:Pyr PTS (periplasm)GLCptspp 1.00L-Lactate dehydrogenase (menaquinone)L_LACD3 0.00mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
The sensitivity of an FBA solution is indicated by either shadow prices or reduced costs. Shadow prices are the derivative of the objective function with respect to the exchange flux of a metabolite. They indicate how much the addition of that metabolite will increase or decrease the objective. Shadow prices give us an indication of the growth-limiting compounds in the medium.
The reduced cost is a quantity similar to the shadow price, but associated with reactions rather than metabolites. Reduced costs are the derivatives of the objective function with respect to an internal reaction, indicating how much each particular reaction affects the objective.
In the COBRApy package, after computing an optimal solution for a model, shadow prices can be accessed for each metabolite through the y attribute (`metabolite.y`) (see [COBRApy documentation](http://cobrapy.readthedocs.org/en/latest/cobra.core.html#module-cobra.core.Metabolite)). Note that the sign of the `y` attribute should be changed to get the standard interpretation of a positive shadow price: an increase in metabolite uptake (relaxing constraint) leads to a positive increase in the objective function (e.g. biomass production).
More information:
+ Price, N. D., Reed, J. L., Palsson, B. Ø., & Correspondence, B. Ø. P. (2004). Genome-Scale Models of Microbial Cells : Evaluating the Consequences of Constraints, 2(November), 886–897. http://doi.org/10.1038/nrmicro1023
+ Goffin, P., van de Bunt, B., Giovane, M., Leveau, J. H. J., Höppener-Ogawa, S., Teusink, B., & Hugenholtz, J. (2010). Understanding the physiology of Lactobacillus plantarum at zero growth. Molecular Systems Biology, 6(413), 413. http://doi.org/10.1038/msb.2010.67
+ Teusink, B., Wiersma, A., Molenaar, D., Francke, C., De Vos, W. M., Siezen, R. J., & Smid, E. J. (2006). Analysis of growth of Lactobacillus plantarum WCFS1 on a complex medium using a genome-scale metabolic model. Journal of Biological Chemistry, 281(52), 40041–40048. http://doi.org/10.1074/jbc.M606263200

The sensitivity of an FBA solution is indicated by either shadow prices or reduced costs. Shadow prices are the derivative of the objective function with respect to the exchange flux of a metabolite. They indicate how much the addition of that metabolite will increase or decrease the objective. Shadow prices give us an indication of the growth-limiting compounds in the medium.

The reduced cost is a quantity similar to the shadow price, but associated with reactions rather than metabolites. Reduced costs are the derivatives of the objective function with respect to an internal reaction, indicating how much each particular reaction affects the objective.

In the COBRApy package, after computing an optimal solution for a model, shadow prices can be accessed for each metabolite through the y attribute (metabolite.y) (see COBRApy documentation). Note that the sign of the y attribute should be changed to get the standard interpretation of a positive shadow price: an increase in metabolite uptake (relaxing constraint) leads to a positive increase in the objective function (e.g. biomass production).

More information:

  • Price, N. D., Reed, J. L., Palsson, B. Ø., & Correspondence, B. Ø. P. (2004). Genome-Scale Models of Microbial Cells : Evaluating the Consequences of Constraints, 2(November), 886–897. http://doi.org/10.1038/nrmicro1023
  • Goffin, P., van de Bunt, B., Giovane, M., Leveau, J. H. J., Höppener-Ogawa, S., Teusink, B., & Hugenholtz, J. (2010). Understanding the physiology of Lactobacillus plantarum at zero growth. Molecular Systems Biology, 6(413), 413. http://doi.org/10.1038/msb.2010.67
  • Teusink, B., Wiersma, A., Molenaar, D., Francke, C., De Vos, W. M., Siezen, R. J., & Smid, E. J. (2006). Analysis of growth of Lactobacillus plantarum WCFS1 on a complex medium using a genome-scale metabolic model. Journal of Biological Chemistry, 281(52), 40041–40048. http://doi.org/10.1074/jbc.M606263200
 
Compute the shadow price of cytosolic proton `h_c` and of glucose `glc__D_c`.

Compute the shadow price of cytosolic proton h_c and of glucose glc__D_c.

In [44]:
 
model.metabolites.h_c.y
Out[44]:
0.25
In [45]:
 
model.metabolites.glc__D_c.y
Out[45]:
-23.500000000000103
 
As expected, the shadow price of glucose is 23.5 mol ATP/ mol glucose, the same value as we have found above.
ATP production is also limited by cellular proton balancing. The shadow price of cytosolic protons (`h_c`) is -0.25, indicating that the increase of 4 mol protons/mol glucose to the system decreases ATP yield by 1 mol ATP/mol glucose. Protons are produced by various metabolic reactions and are also pumped into the cell by the ATP synthase reaction. In order for the system to be at steady-state, an equal number of protons must be pumped out by the electron transport chain reactions or by excreting metabolites with symporters. If more ATP were to be produced by ATP synthase, it would import additional protons that have no way to escape the cell.

As expected, the shadow price of glucose is 23.5 mol ATP/ mol glucose, the same value as we have found above.

ATP production is also limited by cellular proton balancing. The shadow price of cytosolic protons (h_c) is -0.25, indicating that the increase of 4 mol protons/mol glucose to the system decreases ATP yield by 1 mol ATP/mol glucose. Protons are produced by various metabolic reactions and are also pumped into the cell by the ATP synthase reaction. In order for the system to be at steady-state, an equal number of protons must be pumped out by the electron transport chain reactions or by excreting metabolites with symporters. If more ATP were to be produced by ATP synthase, it would import additional protons that have no way to escape the cell.

 
Calculation of NADH and NADPH one at a time can be performed in a similar manner. First, constrain `ATPM` to 0 mmol gDW<sup>-1</sup> h<sup>-1</sup> flux so the cell is not required to produce ATP, and also cannot consume any ATP using this reaction.

Calculation of NADH and NADPH one at a time can be performed in a similar manner. First, constrain ATPM to 0 mmol gDW-1 h-1 flux so the cell is not required to produce ATP, and also cannot consume any ATP using this reaction.

In [46]:
 
# Constrain glucose uptake
glc_exchange.lower_bound = -1
glc_exchange.upper_bound = -1
# Constrain ATPM reaction flux
model.reactions.ATPM.lower_bound = 0
model.reactions.ATPM.upper_bound = 0
 
Add stoichiometrically balanced NADH consuming reactions using the function `model.add_reaction`.
Any arbitrary reaction can be defined in the COBRA package. The easiest way to add a new reaction to an existing model is the following:
+ create a `cobra.Reaction` object and set its id to 'NADH_consume' and set its name attribute.
+ add the reaction object to the model using the `model.add_reaction` function
+ define the reaction equation and metabolites by using the `reaction.build_reaction_from_string` function. A simple string containing the reaction equation using the correct metabolites id's is enough to define the metabolites and their stochiometric coefficients.
+ print the newly defined reaction equation

Add stoichiometrically balanced NADH consuming reactions using the function model.add_reaction.

Any arbitrary reaction can be defined in the COBRA package. The easiest way to add a new reaction to an existing model is the following:

  • create a cobra.Reaction object and set its id to 'NADH_consume' and set its name attribute.
  • add the reaction object to the model using the model.add_reaction function
  • define the reaction equation and metabolites by using the reaction.build_reaction_from_string function. A simple string containing the reaction equation using the correct metabolites id's is enough to define the metabolites and their stochiometric coefficients.
  • print the newly defined reaction equation
In [47]:
 
# Create the reaction object
reaction = cobra.Reaction('NADH_consume')
reaction.name = 'NADH consuming reaction'
# Add the reaction object to the model
model.add_reaction(reaction)
# Define the reaction equation and metabolites using a string. Example met1_c + met2_c -> met3_c
reaction.build_reaction_from_string('nadh_c -> nad_c + h_c', verbose=True)
print(model.reactions.NADH_consume.reaction)
nadh_c --> nad_c + h_c
 
 Set the NADH consuming reaction as the objective using `model.change_objective`.

Set the NADH consuming reaction as the objective using model.change_objective.

In [48]:
 
model.change_objective('NADH_consume')
 
Calculate the optimal solution which should give the maximum yield of NADH. Now the optimal objective value is the flux through the NADH consuming reaction in units of mmol gDW<sup>-1</sup> h<sup>-1</sup>. Because the uptake rate of glucose has been set to exactly -1 mmol gDW<sup>-1</sup> h<sup>-1</sup>, we can obtain easily the ratio of NADH molecules produced per glucose molecules consumed. The result should be 10.29 mol NADH/mol glucose.

Calculate the optimal solution which should give the maximum yield of NADH. Now the optimal objective value is the flux through the NADH consuming reaction in units of mmol gDW-1 h-1. Because the uptake rate of glucose has been set to exactly -1 mmol gDW-1 h-1, we can obtain easily the ratio of NADH molecules produced per glucose molecules consumed. The result should be 10.29 mol NADH/mol glucose.

In [49]:
 
solution = model.optimize()
print('Maximum NADH production rate:', solution.f, 'mol NADH/mol glucose')
Maximum NADH production rate: 10.285714285721184 mol NADH/mol glucose
 
Then, print the shadow price of cytosolic proton (`h_c`) and ATP (`atp_c`).

Then, print the shadow price of cytosolic proton (h_c) and ATP (atp_c).

In [50]:
 
model.metabolites.h_c.y
Out[50]:
0.07142857142857295
In [51]:
 
model.metabolites.atp_c.y
Out[51]:
-14.714285714285722
 
NADH and NADPH production are also ultimately limited by proton balancing. For
maximum NADH yield, the proton shadow price is -0.07 and ATP shadow price 15.4. The protons produced in metabolism are removed by `ATPS4rpp` in reverse (with a negative flux), which consumes ATP and exports protons to the periplasm. The stoichiometry of the network also limits the production of NADH and NADPH. Glucose has 12 electron pairs that can be donated to redox carriers such as NAD+ or NADP+ , but when the TCA cycle is used, two of these electron pairs are used
to reduce the quinone `q8_c` in the succinate dehydrogenase reaction (`SUCDi`), and thus cannot be used to produce NADH or NADPH. The only pathway that can reduce 12 redox carriers with one molecule glucose is the pentose phosphate pathway, but this is infeasible because this pathway generates no ATP, which is needed to pump out the protons that are produced.

NADH and NADPH production are also ultimately limited by proton balancing. For maximum NADH yield, the proton shadow price is -0.07 and ATP shadow price 15.4. The protons produced in metabolism are removed by ATPS4rpp in reverse (with a negative flux), which consumes ATP and exports protons to the periplasm. The stoichiometry of the network also limits the production of NADH and NADPH. Glucose has 12 electron pairs that can be donated to redox carriers such as NAD+ or NADP+ , but when the TCA cycle is used, two of these electron pairs are used to reduce the quinone q8_c in the succinate dehydrogenase reaction (SUCDi), and thus cannot be used to produce NADH or NADPH. The only pathway that can reduce 12 redox carriers with one molecule glucose is the pentose phosphate pathway, but this is infeasible because this pathway generates no ATP, which is needed to pump out the protons that are produced.

 
Repeat the same analysis and compute the maximal yield for NADPH. The result should be 9.36 mol NADH/mol glucose.

Repeat the same analysis and compute the maximal yield for NADPH. The result should be 9.36 mol NADH/mol glucose.

In [52]:
 
# Create the reaction object
reaction = cobra.Reaction('NADPH_consume')
reaction.name = 'NADPH consuming reaction'
# Add the reaction object to the model
model.add_reaction(reaction)
# Define the reaction equation and metabolites using a string. Example A + B -> C
reaction.build_reaction_from_string('nadph_c -> nadp_c + h_c', verbose=True)
print(model.reactions.NADPH_consume.reaction)
# Change objective function to the NADPH_consume reaction
model.change_objective('NADPH_consume')
# Compute optimal solution
solution = model.optimize()
print('Maximum NADPH production rate:', solution.f, 'mol NADPH/mol glucose')
nadph_c --> nadp_c + h_c
Maximum NADPH production rate: 9.363636363636251 mol NADPH/mol glucose
 
### Gene knockouts and gene essentiality

Gene knockouts and gene essentiality

In [53]:
 
# Reload the metabolic model with default values
model = cobra.io.load_json_model('iJO1366.json')
model.change_objective('BIOMASS_Ec_iJO1366_core_53p95M')
# Define aliases for the glucose and oxygen uptake reactions
glc_exchange = model.reactions.get_by_id('EX_glc__D_e')
o2_exchange = model.reactions.get_by_id('EX_o2_e')
 
Compute the growth in the WT strain with the `model.optimize` function. The default conditions are aerobic growth on glucose with uptake rate of 10 mmol gDW<sup>-1</sup> h<sup>-1</sup>.

Compute the growth in the WT strain with the model.optimize function. The default conditions are aerobic growth on glucose with uptake rate of 10 mmol gDW-1 h-1.

In [54]:
 
solution = model.optimize()
print('WT growth rate: {:.3f} h^-1'.format(solution.f))
WT growth rate: 0.982 h^-1
 
#### Gene-protein-reaction rules
Just as growth in different environments can be simulated with FBA, gene knockouts can also be simulated by changing reaction bounds. To simulate the knockout of any gene, its associated reaction or reactions can simply be constrained to not carry flux. By setting both the upper and lower bounds of a reaction to 0 mmol gDW<sup>-1</sup> h<sup>-1</sup> , a reaction is essentially knocked out, and is restricted from carrying flux. The E. coli core model, like many other constraint-based models, contains a list of gene-protein-reaction interactions (GPRs), a list of Boolean rules that dictate which genes are connected with each reaction in the model. When a reaction is catalyzed by isozymes (two different enzymes that catalyze the same reaction), the associated GPR contains an “or” rule, where either of two or more genes may be knocked out but the reaction will not be constrained. For example, the GPR for phosphofructokinase (`PFK`) is “b1723 (pfkB) or b3916 (pfkA),” so according to this Boolean rule, both pfkB and pfkA must be knocked out to restrict this reaction. When a reaction is catalyzed by a protein with multiple essential subunits, the GPR contains an “and” rule, and if any of the genes are knocked out the reaction will be constrained to 0 flux. Succinyl-CoA synthetase (SUCOAS), for example, has the GPR “b0728 (sucC) and b0729 (sucD),” so knocking out either of these genes will restrict this reaction. Some reactions are catalyzed by a single gene product, while others may be associated with ten or more genes in complex associations.
The gene-reaction rules can be accessed with the `gene_reaction_rule` attribute of the reaction. Example:

Gene-protein-reaction rules

Just as growth in different environments can be simulated with FBA, gene knockouts can also be simulated by changing reaction bounds. To simulate the knockout of any gene, its associated reaction or reactions can simply be constrained to not carry flux. By setting both the upper and lower bounds of a reaction to 0 mmol gDW-1 h-1 , a reaction is essentially knocked out, and is restricted from carrying flux. The E. coli core model, like many other constraint-based models, contains a list of gene-protein-reaction interactions (GPRs), a list of Boolean rules that dictate which genes are connected with each reaction in the model. When a reaction is catalyzed by isozymes (two different enzymes that catalyze the same reaction), the associated GPR contains an “or” rule, where either of two or more genes may be knocked out but the reaction will not be constrained. For example, the GPR for phosphofructokinase (PFK) is “b1723 (pfkB) or b3916 (pfkA),” so according to this Boolean rule, both pfkB and pfkA must be knocked out to restrict this reaction. When a reaction is catalyzed by a protein with multiple essential subunits, the GPR contains an “and” rule, and if any of the genes are knocked out the reaction will be constrained to 0 flux. Succinyl-CoA synthetase (SUCOAS), for example, has the GPR “b0728 (sucC) and b0729 (sucD),” so knocking out either of these genes will restrict this reaction. Some reactions are catalyzed by a single gene product, while others may be associated with ten or more genes in complex associations.

The gene-reaction rules can be accessed with the gene_reaction_rule attribute of the reaction. Example:

In [55]:
 
print(model.reactions.PFK.gene_reaction_rule)
print(model.reactions.SUCOAS.gene_reaction_rule)
b3916 or b1723
b0728 and b0729
 
#### Single gene deletion
The COBRA package contains a function called `single_deletion` that uses the GPRs to constrain the correct reactions and computes the growth rate by FBA optimization. For example, growth can be predicted for E. coli growing aerobically on glucose with the gene _zwf_ (id `b1852`), corresponding to the reaction glucose-6-phosphate dehydrogenase (G6PDH2r), knocked out.
More information:
+ COBRApy documentation http://cobrapy.readthedocs.org/en/latest/deletions.html

Single gene deletion

The COBRA package contains a function called single_deletion that uses the GPRs to constrain the correct reactions and computes the growth rate by FBA optimization. For example, growth can be predicted for E. coli growing aerobically on glucose with the gene zwf (id b1852), corresponding to the reaction glucose-6-phosphate dehydrogenase (G6PDH2r), knocked out.

More information:

 
First, print the reaction list associated with the _zwf_ gene (id `b1852`). Gene object can be accessed through the `model.genes` dictionary. The `reactions` attribute contains all the reactions that are associated with the gene as a python frozen set. Use a for loop to print all the reactions and their name. In the case of gene `b1852`, there is only one associated reaction.

First, print the reaction list associated with the zwf gene (id b1852). Gene object can be accessed through the model.genes dictionary. The reactions attribute contains all the reactions that are associated with the gene as a python frozen set. Use a for loop to print all the reactions and their name. In the case of gene b1852, there is only one associated reaction.

In [56]:
 
for reac in model.genes.b1852.reactions:
    print(reac, ' ', reac.name)
G6PDH2r   Glucose 6-phosphate dehydrogenase
 
We have also defined above a function to print out the most relevant information about a gene. It takes as argument the gene object. Try it with the same gene `b1852`.

We have also defined above a function to print out the most relevant information about a gene. It takes as argument the gene object. Try it with the same gene b1852.

In [57]:
 
print_gene_info(model.genes.b1852)
cobra_id:  b1852
name:  zwf
associated reactions:
G6PDH2r ,  Glucose 6-phosphate dehydrogenase

 
Compute the growth rate for the strain with gene _zwf_ gene (id `b1852`) knocked out. The `single_deletion` function is part of the subpackage `cobra.flux_analysis`. It takes as first argument the model object and as second argument a set of gene objects (hint: use `{}` to pass a set of objects).

Compute the growth rate for the strain with gene zwf gene (id b1852) knocked out. The single_deletion function is part of the subpackage cobra.flux_analysis. It takes as first argument the model object and as second argument a set of gene objects (hint: use {} to pass a set of objects).

In [58]:
 
growth_rate, status = cobra.flux_analysis.single_gene_deletion(model, {model.genes.b1852} )
print('zwf- growth rate: {:.3f}, status {}'.format(growth_rate['b1852'], status['b1852']))
zwf- growth rate: 0.976, status optimal
 
The FBA predicted growth rate of the mutant strain is 0.976 h<sup>-1</sup>, which is slightly lower than the growth rate of 0.982 h<sup>-1</sup> for wild-type E. coli because the cell can no longer use the oxidative branch of the pentose phosphate pathway to generate NADPH.

The FBA predicted growth rate of the mutant strain is 0.976 h-1, which is slightly lower than the growth rate of 0.982 h-1 for wild-type E. coli because the cell can no longer use the oxidative branch of the pentose phosphate pathway to generate NADPH.

 
Using FBA to predict the phenotypes of gene knockouts is especially useful in predicting essential genes. When no alternative pathway or isoenzyme exist to substitute the deleted reactions associated to the knocked out gene, the reported growth rate is zero and the gene is reported as essential in the analysis.
Print the reactions associated with gene _icd_ (`b1136`).

Using FBA to predict the phenotypes of gene knockouts is especially useful in predicting essential genes. When no alternative pathway or isoenzyme exist to substitute the deleted reactions associated to the knocked out gene, the reported growth rate is zero and the gene is reported as essential in the analysis.

Print the reactions associated with gene icd (b1136).

In [59]:
 
for reac in model.genes.b1136.reactions:
    print(reac, ' ', reac.name, ' ', reac.reaction)
ICDHyr   Isocitrate dehydrogenase (NADP)   icit_c + nadp_c <=> co2_c + akg_c + nadph_c
 
Compute the single gene deletion growth rate of gene _icd_ (`b1136`).

Compute the single gene deletion growth rate of gene icd (b1136).

In [60]:
 
growth_rate, status = cobra.flux_analysis.single_gene_deletion(model, {model.genes.b1136} )
print('icd- growth rate: {:.3f}, status {}'.format(growth_rate['b1136'], status['b1136']))
icd- growth rate: -0.000, status optimal
 
The gene _icd_ encodes for the enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing $\alpha$-ketoglutarate ($\alpha$-KG) and CO2. The reaction is part of the TCA cycle. Although the TCA cycle allows maximal energy yield from degradation of glucose, its more critical role is to supply precursors for biosynthetic pathways that branch from $\alpha$-ketoglutarate, oxaloacetate, and succinyl CoA. There is only one way to make $\alpha$-KG, so the segment of the cycle leading to $\alpha$-KG is essential.
Draw the metabolic map with the knocked-out reaction highlighted in red.

The gene icd encodes for the enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing α-ketoglutarate (α-KG) and CO2. The reaction is part of the TCA cycle. Although the TCA cycle allows maximal energy yield from degradation of glucose, its more critical role is to supply precursors for biosynthetic pathways that branch from α-ketoglutarate, oxaloacetate, and succinyl CoA. There is only one way to make α-KG, so the segment of the cycle leading to α-KG is essential.

Draw the metabolic map with the knocked-out reaction highlighted in red.

In [61]:
 
model_modified = model.copy()
model_modified.reactions.ICDHyr.delete()
metabolicMap = escher.Builder(map_name='iJO1366.Central metabolism',
                              model=model_modified,
                              # in the map, highlight all reactions that are missing from the model
                              highlight_missing=True,
                              # only show the primary metabolites
                              hide_secondary_metabolites=True)
metabolicMap.display_in_notebook()
Out[61]:
Malate dehydrogenaseMDHNitrite Reductase (Ubiquinole-8, periplasm)NTRIR3pp33NADPH Quinone Reductase (2-Demethylmenaquinone-8)NADPHQR4NADH dehydrogenase (menaquinone-8 & 3 protons) (periplasm)NADH17ppL-malate transport out via proton antiport (periplasm)MALt3ppD-lactate transport via proton symport (periplasm)D_LACt2ppGlucose-1-phosphataseG1PPppTrans-aconitate methyltransferaseACONMTAcetaldehyde transport via diffusion (extracellular to periplasm)ACALDtexGlycolate oxidaseGLYCTO3Aconitate isomerase (spontaneous)ACONIsCytochrome oxidase bd (menaquinol-8: 2 protons) (periplasm)CYTBD2pp0.5Phosphoenolpyruvate carboxylasePPCFructose 6-phosphate transport via diffusion (extracellular to periplasm)F6PtexMalate synthaseMALSHydrogenase (Demethylmenaquinone-8: 2 protons) (periplasm)HYD3pp22Sedoheptulose 1,7-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA3Ethanol reversible transport via diffusion (periplasm)ETOHtrppCytochrome oxidase bd (ubiquinol-8: 2 protons) (periplasm)CYTBDpp0.5Fumarate transport via proton symport (2 H) (periplasm)FUMt2_2ppGlycogen phosphorylaseGLCPNitrate reductase (Menaquinol-8) (periplasm)NO3R2bppNADH dehydrogenase (demethylmenaquinone-8 & 3 protons) (periplasm)NADH18ppDsbA protein reoxidation reaction (aerobic)DSBAO1Trimethylamine N-oxide reductase (demethylmenaquinol 8) (periplasm)TMAOR2ppCitrate synthaseCSGlucose-1-phosphate adenylyltransferaseGLGCGlycerol transport via channel (periplasm)GLYCtppGlycolate oxidaseGLYCTO4Glucose-6-phosphate isomerasePGIGlycerol transport via diffusion (extracellular to periplasm)GLYCtexQuinol monooxygenase (menaquinol 8)QMO322Hydroxyacylglutathione hydrolaseGLYOXPhosphoglycerate kinasePGKFumarate transport via diffusion (extracellular to periplasm)FUMtexCatalaseCAT22Ethanol transport via diffusion (extracellular to periplasm)ETOHtexHydrogen transport diffusion (periplasm)H2tppSuperoxide dismutaseSPODMpp22Glycerol-3-phosphate dehydrogenase (ubiquinone-8)G3PD5PhosphoglucomutasePGMTGlucose 6-phosphate dehydrogenaseG6PDH2rAcetyl-CoA synthetaseACSGlycerol kinaseGLYK2-oxoglutarate reversible transport via symport (periplasm)AKGt2rppMalate transport via proton symport (2 H) (periplasm)MALt2_2pp6-phosphogluconolactonasePGL(R)-Propane-1,2-diol facilitated transport (periplasm)12PPDRtppDimethyl sulfoxide transport via diffusion (periplasm)DMSOtppATP synthase (four protons for one ATP) (periplasm)ATPS4rpp43NADH dehydrogenase (ubiquinone-8 & 3 protons) (periplasm)NADH16ppAcetate kinaseACKrGlycogen debranching enzyme (bglycogen -> glycogen)GLDBRAN2Ribose-5-phosphate isomeraseRPID-xylose transport in via proton symport (periplasm)XYLt2ppD-glucose 1-phosphate transport via diffusionG1PtexMalate transport via diffusion (extracellular to periplasm)MALtexCytochrome oxidase bo3 (ubiquinol-8: 4 protons) (periplasm)CYTBO3_4pp0.5Dimethyl sulfoxide reductase (Menaquinol 8) (periplasm)DMSOR1ppD-fructose transport via PEP:Pyr PTS (periplasm)FRUptsppPolyphosphate kinasePPK2rL-Lactate dehydrogenase (ubiquinone)L_LACD2Pyruvate kinasePYKQuinol monooxygenase (Ubiquinol-8)QMO2L-lactate reversible transport via proton symport (periplasm)L_LACt2rppNADH dehydrogenase (menaquinone-8 & 0 protons)NADH10Glycerol dehydrogenaseGLYCDxMalate transport via proton symport (3 H) (periplasm)MALt2_3ppDihydroxyacetone phosphotransferaseDHAPTCO2 transport via diffusion (extracellular to periplasm)CO2texNitrate reductase (Ubiquinol-8)NO3R1bppDsbA protein reoxidation reaction (anaerobic)DSBAO2Sn-Glycerol 3-phosphate transport via ABC system (periplasm)GLYC3PabcppPhosphoenolpyruvate carboxykinasePPCKL-lactate transport via diffusion (extracellular to periplasm)L_LACtexPyruvate dehydrogenasePDHMalic enzyme (NADP)ME2Acetaldehyde reversible transport (periplasm)ACALDtppD-fructose transport via diffusion (extracellular to periplasm)FRUtexD-xylose transport via ABC system (periplasm)XYLabcppFumarate reductaseFRD3Inorganic triphosphatasePPA2Acetate reversible transport via proton symport (periplasm)ACt2rppHydrogenase (menaquinone8: 2 protons) (periplasm)HYD2pp22Pyruvate oxidasePOXNADPH Quinone Reductase (Ubiquinone-8)NADPHQR2Aconitase (half-reaction B, Isocitrate hydro-lyase)ACONTbCitrate transport via diffusion (extracellular to periplasm)CITtexD-ribose transport via ABC system (periplasm)RIBabcppFumaraseFUM2-dehydro-3-deoxy-phosphogluconate aldolaseEDAPyruvate formate lyasePFLInorganic diphosphatasePPA2Nitrate reductase (Ubiquinol-8) (periplasm)NO3R1ppGlycogen phosphorylaseGLCP2Trimethylamine N-oxide reductase (menaquinol 8) (periplasm)TMAOR1ppNADH dehydrogenase (ubiquinone-8 )NADH5D-lactate dehydrogenaseLDH_DLacaldehyde reductase (R-propane-1,2-diol forming)LCARRPhosphoglycerate mutasePGMRibulose 5-phosphate 3-epimeraseRPEFumarate reductaseFRD2NADPH Quinone Reductase (Menaquinone-8)NADPHQR3Glycerol-3-phosphate transport via diffusion (extracellular to periplasm)GLYC3PtexPhosphoenolpyruvate synthasePPS1,4-alpha-glucan branching enzyme (glycogen -> bglycogen)GLBRAN2Glycerol-3-phosphate dehydrogenase (demethylmenaquinone-8)G3PD7D-glucose transport via PEP:Pyr PTS (periplasm)GLCptsppTrimethylamine N-oxide reductase (demethylmenaquinol 8)TMAOR2Formate Dehydrogenase (menaquinone-8) (periplasm)FDH5ppSuperoxide dismutaseSPODM22Succinate transport via proton symport (2 H) (periplasm)SUCCt2_2ppSuccintate transport via proton symport (3 H) (periplasm)SUCCt2_3ppFructose-bisphosphataseFBPHydrogenase (ubiquinone-8: 2 protons) (periplasm)HYD1pp22Triose-phosphate isomeraseTPI(R)-Propane-1,2-diol transport via diffusion (extracellular to periplasm)12PPDRtexIsocitrate lyaseICLIsocitrate dehydrogenase (NADP)ICDHyrD-lactate transport via diffusion (extracellular to periplasm)D_LACtexMalate dehydrogenase (menaquinone 8 as acceptor)MDH3Formate transport via diffusion (extracellular to periplasm)FORtexEnolaseENOL-Lactate dehydrogenase (menaquinone)L_LACD3Glycerol-3-phosphataseG3PTGlucose dehydrogenase (ubiquinone-8 as acceptor) (periplasm)GLCDppD-glucose transport in via proton symport (periplasm)GLCt2ppRibokinaseRBKPhosphotransacetylasePTArGlyceraldehyde-3-phosphate dehydrogenaseGAPDCitrate transport out via proton antiport (periplasm)CITt3ppSuccinyl-CoA synthetase (ADP-forming)SUCOASHydrogen transport via diffusion (extracellular to periplasm)H2texAconitase (half-reaction A, Citrate hydro-lyase)ACONTaPhosphofructokinasePFKD-Lactaldehyde:NAD+ 1-oxidoreductaseLALDO2xAcetate transport via diffusion (extracellular to periplasm)ACtexATP maintenance requirementATPMPhosphofructokinase (s7p)PFK_3Methylglyoxal synthaseMGSANADH dehydrogenase (demethylmenaquinone-8 & 0 protons)NADH9Fructose-6-phosphate transport via phosphate antiport (periplasm)F6Pt6_2ppNitrite Reductase (NADH)NTRIR2xCitrate transport via succinate antiport (periplasm)CITt7ppFructose 6-phosphate aldolaseF6PAMalate dehydrogenase (ubiquinone 8 as acceptor)MDH2Glycerol-3-phosphate : phosphate antiporter (periplasm)GLYC3Pt6ppPyruvate reversible transport via proton symport (periplasm)PYRt2rppGlycolate oxidaseGLYCTO2TransketolaseTKT1NAD(P) transhydrogenase (periplasm)THD2pp22Succinate transport out via proton antiport (periplasm)SUCCt3ppPolyphosphate kinasePPKrAlcohol dehydrogenase (ethanol)ALCD2xSuccinate transport via diffusion (extracellular to periplasm)SUCCtexDimethyl sulfoxide reductase (Demethylmenaquinol 8)DMSOR2Aldehyde dehydrogenase (acetaldehyde, NAD)ALDD2xGlycerol-3-phosphate dehydrogenase (NADP)G3PD2Xylose isomeraseXYLI1Nitrite Reductase (Menaquinole-8, periplasm)NTRIR4pp33Citrate lyaseCITLFormate transport via proton symport (uptake only, periplasm)FORt2ppGlucose transport via diffusion (extracellular to periplasm)GLCtex_copy1Pyruvate transport via diffusion (extracellular to periplasm)PYRtexSuccinate dehydrogenase (irreversible)SUCDiFormate transport via diffusion (cytoplasm to periplasm)FORtppiTransaldolaseTALATransketolaseTKT2D-xylose transport via diffusion (extracellular to periplasm)XYLtex2-Oxogluterate dehydrogenaseAKGDHAlpha-ketoglutarate transport via diffusion (extracellular to periplasm)AKGtexNitrate reductase (Menaquinol-8) (periplasm)NO3R2ppLactoylglutathione lyaseLGTHLAldehyde dehydrogenase (acetaldehyde, NADP)ALDD2y6-phosphogluconate dehydrataseEDDFructose-1-phosphate kinaseFRUKFormate dehydrogenase (quinone-8) (periplasm)FDH4ppMalate oxidaseMOXCO2 transporter via diffusion (periplasm)CO2tppMalic enzyme (NAD)ME1XylulokinaseXYLKGlucose-6-phosphate transport via phosphate antiport (periplasm)G6Pt6_2ppNAD transhydrogenaseNADTRHDGlycerol-3-phosphate dehydrogenase (menaquinone-8)G3PD6Phosphogluconate dehydrogenaseGNDHexokinase (D-glucose:ATP)HEX1Dimethyl sulfoxide reductase (Menaquinol 8)DMSOR1Fumarate transport via proton symport (3 H) (periplasm)FUMt2_3ppTrimethylamine N-oxide reductase (menaquinol 8)TMAOR1Fructose-bisphosphate aldolaseFBAGlucose-6-phosphate phosphataseG6PPRibose transport via diffusion (extracellular to periplasm)RIBtexFructose transport via PEP:Pyr PTS (f6p generating) (periplasm)FRUpts2ppAcetaldehyde dehydrogenase (acetylating)ACALDHCO3 equilibration reactionHCO3EFormate-hydrogen lyaseFHLGlycogen synthase (ADPGlc)GLCS1Glucose 6-phosphate transport via diffusion (extracellular to periplasm)G6PtexOxaloacetate decarboxylaseOAADCDimethyl sulfoxide reductase (Demethylmenaquinol 8) (periplasm)DMSOR2ppD-lactate dehydrogenaseLDH_D2D-lactate dehydrogenaseLDH_D2L-Lactate dehydrogenase (ubiquinone)L_LACD2D-glucose transport via PEP:Pyr PTS (periplasm)GLCptsppL-Lactate dehydrogenase (menaquinone)L_LACD3mal__L_cL-MalateNicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedH+oaa_cOxaloacetateq8h2_cUbiquinol-8no2_pNitriteH+H2Oq8_cUbiquinone-8nh4_pAmmonium2dmmq8_c2-Demethylmenaquinone 8H+nadph_cNicotinamide adenine dinucleotide phosphate - reduced2dmmql8_c2-Demethylmenaquinol 8nadp_cNicotinamide adenine dinucleotide phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+mqn8_cMenaquinone 8nad_cNicotinamide adenine dinucleotideH+mql8_cMenaquinol 8H+H+mal__L_pL-Malatelac__D_pD-LactateH+lac__D_cD-LactateH+g1p_pD-Glucose 1-phosphateH2OPhosphateglc__D_pD-Glucoseacon_T_cTrans-AconitateS-Adenosyl-L-methionineS-Adenosyl-L-homocysteineaconm_cE-3-carboxy-2-pentenedioate 6-methyl esteracald_eAcetaldehydeacald_pAcetaldehydeglyclt_cGlycolateglx_cGlyoxylateacon_C_cCis-AconitateH+o2_cO2h2o_cH2OH+pep_cPhosphoenolpyruvateH2OCO2H+Phosphatef6p_eD-Fructose 6-phosphatef6p_pD-Fructose 6-phosphateH2OAcetyl-CoAglx_cGlyoxylateH+Coenzyme Ah2_cH2h_cH+h_pH+s17bp_cSedoheptulose 1,7-bisphosphatee4p_cD-Erythrose 4-phosphatedhap_cDihydroxyacetone phosphateetoh_pEthanoletoh_cEthanolH+o2_cO2H2OH+H+fum_pFumarateH+fum_cFumaratePhosphateglycogen_cGlycogeng1p_cD-Glucose 1-phosphateno3_pNitrateno2_pNitriteH2OH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)tmao_pTrimethylamine N-oxideH+H2Otma_pTrimethylamineaccoa_cAcetyl-CoAH2Ocit_cCitrateH+Coenzyme AATPH+Diphosphateadpglc_cADPglucoseglyc_cGlycerolglyc_pGlycerolglyclt_cGlycolateglx_cGlyoxylateg6p_cD-Glucose 6-phosphatef6p_cD-Fructose 6-phosphateglyc_eGlycerolo2_cO2H+o2s_cSuperoxide anionH2Olgt__S_c(R)-S-LactoylglutathioneH+Reduced glutathioneATP3pg_c3-Phospho-D-glycerateADP13dpg_c3-Phospho-D-glyceroyl phosphatefum_eFumarateh2o2_cHydrogen peroxideh2o_cH2Oo2_cO2etoh_eEthanolh2_pH2h2_cH2h_pH+o2s_pSuperoxide anionh2o2_pHydrogen peroxideo2_pO2glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reduced6pgl_c6-phospho-D-glucono-1,5-lactoneH+ac_cAcetateATPCoenzyme AAMPDiphosphateATPH+glyc3p_cGlycerol 3-phosphateADPH+akg_p2-OxoglutarateH+akg_c2-OxoglutarateH+H+H2O6pgc_c6-Phospho-D-gluconateH+12ppd__R_p(R)-Propane-1,2-diol12ppd__R_c(R)-Propane-1,2-dioldmso_pDimethyl sulfoxidedmso_cDimethyl sulfoxideh_pH+adp_cADPpi_cPhosphateh_cH+atp_cATPh2o_cH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideH+ATPADPactp_cAcetyl phosphatebglycogen_cBranching glycogenr5p_cAlpha-D-Ribose 5-phosphateru5p__D_cD-Ribulose 5-phosphateH+xyl__D_pD-Xylosexyl__D_cD-XyloseH+g1p_eD-Glucose 1-phosphatemal__L_eL-Malateo2_cO2H+H2OH+dmso_pDimethyl sulfoxideH2Odms_pDimethyl sulfidePhosphoenolpyruvatefru_pD-Fructosef1p_cD-Fructose 1-phosphatePyruvateATPppi_cDiphosphatepppi_cInorganic triphosphateADPlac__L_cL-LactateUbiquinone-8Ubiquinol-8ADPH+ATPO2Superoxide anionH+H+lac__L_pL-LactateH+nadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotidedha_cDihydroxyacetoneNicotinamide adenine dinucleotide - reducedH+H+H+PhosphoenolpyruvatePyruvateco2_eCO2co2_pCO2no3_pNitrateH2Ono2_pNitritedsbard_pPeriplasmic protein disulfide isomerase I (reduced)dsbaox_pPeriplasmic protein disulfide isomerase I (oxidized)H2Oglyc3p_pGlycerol 3-phosphateATPH+PhosphateADPATPCO2ADPlac__L_eL-LactateNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2Nicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedacald_cAcetaldehydefru_eD-FructoseH2OATPADPPhosphateH+2-Demethylmenaquinol 8succ_cSuccinate2-Demethylmenaquinone 8H2OH+PhosphateH+ac_pAcetateH+h2_cH2h_cH+h_pH+pyr_cPyruvateH2OCO2ac_cAcetatenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateH2Oicit_cIsocitratecit_eCitratecit_pCitraterib__D_pD-RiboseH2OATPPhosphateADPrib__D_cD-RiboseH+H2O2ddg6p_c2-Dehydro-3-deoxy-D-gluconate 6-phosphateg3p_cGlyceraldehyde 3-phosphateCoenzyme Afor_cFormateH2OH+pi_cPhosphateno3_cNitrateH+H+no2_cNitriteH2OPhosphateH+tmao_pTrimethylamine N-oxidetma_pTrimethylamineH2Onadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotideNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide - reducedlald__D_cD-LactaldehydeNicotinamide adenine dinucleotide2pg_cD-Glycerate 2-phosphatexu5p__D_cD-Xylulose 5-phosphateMenaquinol 8Menaquinone 8nadph_cNicotinamide adenine dinucleotide phosphate - reducedH+nadp_cNicotinamide adenine dinucleotide phosphateglyc3p_eGlycerol 3-phosphateATPH2OAMPPhosphateH+glyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphatePhosphoenolpyruvatePyruvatetmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylaminefor_pFormateH+co2_pCO2H+o2s_cSuperoxide anionh_cH+h2o2_cHydrogen peroxideo2_cO2succ_pSuccinateH+H+H+H+fdp_cD-Fructose 1,6-bisphosphateH2OPhosphateh2_cH2h_cH+h_pH+12ppd__R_e(R)-Propane-1,2-diolNicotinamide adenine dinucleotide phosphateCO2Nicotinamide adenine dinucleotide phosphate - reducedlac__D_eD-LactateMenaquinone 8Menaquinol 8for_eFormatefor_pFormateH2OH2OPhosphateglc__D_pD-GlucoseH2OH+glcn_pD-GluconateH+H+glc__D_cD-GlucoseATPADPH+PhosphateCoenzyme APhosphateNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedH+H+Coenzyme AATPPhosphatesuccoa_cSuccinyl-CoAADPh2_eH2ATPADPH+Nicotinamide adenine dinucleotide - reducedH+mthgxl_cMethylglyoxalNicotinamide adenine dinucleotideac_eAcetateatp_cATPH2Oadp_cADPH+PhosphateATPs7p_cSedoheptulose 7-phosphateADPH+Phosphatenadh_cNicotinamide adenine dinucleotide - reducedH+nad_cNicotinamide adenine dinucleotidePhosphatePhosphateNicotinamide adenine dinucleotide - reducedH+no2_cNitriteNicotinamide adenine dinucleotidenh4_cAmmoniumH2Olac__L_cL-Lactatepyr_cPyruvateSuccinateSuccinateUbiquinone-8Ubiquinol-8PhosphatePhosphateH+pyr_pPyruvateH+glyclt_cGlycolateglx_cGlyoxylateh_pH+nadh_cNicotinamide adenine dinucleotide - reducednadp_cNicotinamide adenine dinucleotide phosphateh_cH+nad_cNicotinamide adenine dinucleotidenadph_cNicotinamide adenine dinucleotide phosphate - reducedH+H+ATPADPNicotinamide adenine dinucleotideH+Nicotinamide adenine dinucleotide - reducedsucc_eSuccinateH2Odms_cDimethyl sulfideNicotinamide adenine dinucleotideH2ONicotinamide adenine dinucleotide - reducedH+Nicotinamide adenine dinucleotide phosphateH+Nicotinamide adenine dinucleotide phosphate - reducedxylu__D_cD-XyluloseH+no2_pNitritenh4_pAmmoniumH2OAcetateH+H+glc__D_eD-Glucosepyr_ePyruvateUbiquinone-8Ubiquinol-8xyl__D_eD-XyloseNicotinamide adenine dinucleotideCoenzyme ANicotinamide adenine dinucleotide - reducedCO2akg_e2-OxoglutarateH+no3_cNitrateH+no2_cNitriteH2ONicotinamide adenine dinucleotide phosphateH2ONicotinamide adenine dinucleotide phosphate - reducedH+H2OATPH+ADPH+for_pFormateco2_pCO2H+O2Hydrogen peroxideco2_cCO2Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide - reducedCO2ATPH+ADPPhosphateg6p_pD-Glucose 6-phosphatePhosphateglyc3p_cGlycerol 3-phosphatedhap_cDihydroxyacetone phosphateNicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide phosphate - reducedCO2ATPADPH+dmso_cDimethyl sulfoxidedms_cDimethyl sulfideH2OH+H+tmao_cTrimethylamine N-oxideH+H2Otma_cTrimethylamineH2OPhosphaterib__D_eD-RibosePhosphoenolpyruvatePyruvateNicotinamide adenine dinucleotideCoenzyme AH+Nicotinamide adenine dinucleotide - reducedco2_cCO2h2o_cH2Oh_cH+hco3_cBicarbonateH+CO2H+ADPg6p_eD-Glucose 6-phosphateH+CO2H2Odms_pDimethyl sulfidepyr_cPyruvatelac__D_cD-LactateUbiquinol-8Ubiquinone-8pyr_cPyruvatelac__L_cL-LactateD-GlucoseD-Glucose 6-phosphateMenaquinone 8pyr_cPyruvateMenaquinol 8Nitrite ReductaseTranshydrogenaseCarbonateMenaquinone Reduction/OxidationATPSynthaseDemethylmenaquinone Reduction/OxidationUbiquinone Reduction/OxidationATP MaintenanceOxidative Stress
 
More information:
+ Kim, J., & Copley, S. D. (2007). Why metabolic enzymes are essential or nonessential for growth of Escherichia coli K12 on glucose. Biochemistry, 46(44), 12501–12511. http://doi.org/10.1021/bi7014629
<img src="Images/kim2007_metabolic_map_essential_genes.png" width="720" />
Legend: _Overview of the central metabolic pathways of E. coli. Pathways are indicated by shading as follows: green for the Embden- Myerhof-Parnase pathway, yellow for the pentose phosphate pathway, pink for the Entner-Doudoroff pathway, and blue for the TCA cycle. Steps catalyzed by enzymes that that are essential for growth on glucose are denoted with red arrows, and the genes are colored red. Genes encoding subunits of multisubunit enzymes are enclosed in brackets. Where deletion of genes encoding two isozymes results in loss of the ability to grow on glucose, the genes are colored blue._

More information:

  • Kim, J., & Copley, S. D. (2007). Why metabolic enzymes are essential or nonessential for growth of Escherichia coli K12 on glucose. Biochemistry, 46(44), 12501–12511. http://doi.org/10.1021/bi7014629

Legend: Overview of the central metabolic pathways of E. coli. Pathways are indicated by shading as follows: green for the Embden- Myerhof-Parnase pathway, yellow for the pentose phosphate pathway, pink for the Entner-Doudoroff pathway, and blue for the TCA cycle. Steps catalyzed by enzymes that that are essential for growth on glucose are denoted with red arrows, and the genes are colored red. Genes encoding subunits of multisubunit enzymes are enclosed in brackets. Where deletion of genes encoding two isozymes results in loss of the ability to grow on glucose, the genes are colored blue.

 
Because FBA can compute phenotypes very quickly, it is feasible to use it for large scale computational screens for gene essentiality, including screens for two or more simultaneous knockouts.
Compute the growth rate of all single gene deletions by passing the list of all genes to the `single_deletion` function, part of the `cobra.flux_analysis` module.

Because FBA can compute phenotypes very quickly, it is feasible to use it for large scale computational screens for gene essentiality, including screens for two or more simultaneous knockouts.

Compute the growth rate of all single gene deletions by passing the list of all genes to the single_deletion function, part of the cobra.flux_analysis module.

In [62]:
 
growth_rates, statuses = cobra.flux_analysis.single_gene_deletion(model, model.genes[:])
list(growth_rates.items())[:30]
Out[62]:
[('b2425', 0.98237181256169),
 ('b4544', 0.9823718127267657),
 ('b4067', 0.9823718127259274),
 ('b0306', 0.9823718127306105),
 ('b0684', 0.9823718127265946),
 ('b3430', 0.9823718127271323),
 ('b2024', 1.8562449462073024e-13),
 ('b2750', -4.734378085864711e-14),
 ('b2280', 0.8735946118755241),
 ('b2943', 0.9823718127268722),
 ('b4153', 0.9823718127266269),
 ('b0805', 0.9823718127265946),
 ('b1014', 0.98237181272579),
 ('b2285', 0.8735946118755241),
 ('b4031', 0.9823718127268695),
 ('b4111', 0.9823718127275104),
 ('b0404', 0.9823718127273112),
 ('b0775', 0.0),
 ('b0104', 0.9823718127270709),
 ('b1247', 0.9823718127273741),
 ('b3619', 0.9823718122374717),
 ('b0038', 0.9823718127275104),
 ('b1208', 0.0),
 ('b0997', 0.982371812722317),
 ('b3426', 0.9823718127273451),
 ('b0662', 0.9823718127250362),
 ('b3290', 0.9823718127306105),
 ('b2663', 0.9823718127270442),
 ('b0729', 0.9794797645375769),
 ('b3502', 0.9823718127269341)]
 
Then, count the number of single gene knockouts that are essential and non-essential. The relatively small fraction of genes that are essential shows the built-in robustness of E. coli metabolism to single-gene deletions.

Then, count the number of single gene knockouts that are essential and non-essential. The relatively small fraction of genes that are essential shows the built-in robustness of E. coli metabolism to single-gene deletions.

In [63]:
 
# We convert the lists to a pandas dataframe for easier data manipulation
single_gene_deletion_df = pandas.DataFrame.from_dict({"growth_rates": growth_rates, "status": statuses})
growth_rate_threshold = 1e-5
print('Nb of essential genes: ',    len(single_gene_deletion_df[single_gene_deletion_df['growth_rates'] <= growth_rate_threshold]))
print('Nb of non-essential genes: ',len(single_gene_deletion_df[single_gene_deletion_df['growth_rates'] >  growth_rate_threshold]))
Nb of essential genes:  208
Nb of non-essential genes:  1159
 
#### Double gene deletions (synthetic lethals)
FBA analysis can also be used to compute the effects of knocking down pairs of genes. Synthetic lethals (SL) refer to pairs of non‐essential genes whose simultaneous deletion is lethal. Synthetic gene lethality can arise for a variety of reasons. For example, two gene protein products can be interchangeable with respect to an essential function (isozymes), act in the same essential pathway (with each mutation decreasing the flux through that pathway), or operate in two separate pathways with redundant or complementary essential functions. The study of synthetic lethality plays a pivotal role in elucidating functional associations between genes and gene function predictions.
The identified SL pairs are phenotypically classified into two types. The first type includes the ones that yield auxotrophic strains that can be rescued through the supply of missing nutrients (i.e. amino acids or other compounds), whereas the second type includes those that lack essential functionalities that cannot be restored by adding extra components to the growth medium.
More information:
+ COBRApy documentation http://cobrapy.readthedocs.org/en/latest/deletions.html#double-deletions
+ Suthers, P. F., Zomorrodi, A., & Maranas, C. D. (2009). Genome-scale gene/reaction essentiality and synthetic lethality analysis. Molecular Systems Biology, 5(301), 1–17. http://doi.org/10.1038/msb.2009.56
+ Güell, O., Sagués, F., & Serrano, M. Á. (2014). Essential plasticity and redundancy of metabolism unveiled by synthetic lethality analysis. PLoS Computational Biology, 10(5), e1003637. http://doi.org/10.1371/journal.pcbi.1003637

Double gene deletions (synthetic lethals)

FBA analysis can also be used to compute the effects of knocking down pairs of genes. Synthetic lethals (SL) refer to pairs of non‐essential genes whose simultaneous deletion is lethal. Synthetic gene lethality can arise for a variety of reasons. For example, two gene protein products can be interchangeable with respect to an essential function (isozymes), act in the same essential pathway (with each mutation decreasing the flux through that pathway), or operate in two separate pathways with redundant or complementary essential functions. The study of synthetic lethality plays a pivotal role in elucidating functional associations between genes and gene function predictions.

The identified SL pairs are phenotypically classified into two types. The first type includes the ones that yield auxotrophic strains that can be rescued through the supply of missing nutrients (i.e. amino acids or other compounds), whereas the second type includes those that lack essential functionalities that cannot be restored by adding extra components to the growth medium.

More information:

 
As an example of the first category of synthetic lethal pair, compute the growth rates of an E. coli strain lacking both cysteine synthase genes _cysK_ (`b2414`), _cysM_ (`b2421`). Double gene deletions can be computed with the `double_deletion` function of the `cobra.flux_analysis` module. The functions takes as argument the cobra model, the list of genes to delete, and the optional argument `return_frame`. The latter optional, when set to `True`, return a pandas frame.
Compute the growth rates for the double deletion.

As an example of the first category of synthetic lethal pair, compute the growth rates of an E. coli strain lacking both cysteine synthase genes cysK (b2414), cysM (b2421). Double gene deletions can be computed with the double_deletion function of the cobra.flux_analysis module. The functions takes as argument the cobra model, the list of genes to delete, and the optional argument return_frame. The latter optional, when set to True, return a pandas frame.

Compute the growth rates for the double deletion.

In [64]:
 
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b2414, model.genes.b2421}, return_frame=True)
print('cysK- cysM- double knockout growth rates:')
double_deletion_results
cysK- cysM- double knockout growth rates:
Out[64]:
b2421 b2414
b2421 9.823718e-01 1.916506e-12
b2414 1.916506e-12 9.823718e-01
 
The pair of genes form a synthetic lethal pair, since the growth rate is almost normal when deleting only one of the two genes, while the simultaneous deletion of both genes leads to growth arrest.
The growth can be rescued in silico through the supplementation of the growth medium by L-cysteine (`cys__L_e`). Add this metabolite to the medium by changing the lower bound of its exchange reaction to a small negative amount (reminder: uptake rate are negative) and repeat the double deletion analysis. Observe what happens when changing the uptake rate from -0.05 to -0.5.

The pair of genes form a synthetic lethal pair, since the growth rate is almost normal when deleting only one of the two genes, while the simultaneous deletion of both genes leads to growth arrest.

The growth can be rescued in silico through the supplementation of the growth medium by L-cysteine (cys__L_e). Add this metabolite to the medium by changing the lower bound of its exchange reaction to a small negative amount (reminder: uptake rate are negative) and repeat the double deletion analysis. Observe what happens when changing the uptake rate from -0.05 to -0.5.

In [65]:
 
# Supplement the medium with L-cysteine
model.reactions.EX_cys__L_e.lower_bound = -0.2
# Compute double deletion growth rates
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b2414, model.genes.b2421}, return_frame=True)
print('cysK- cysM- double knockout growth rates with cysteine-supplemented medium:')
# Set back to the default value
model.reactions.EX_cys__L_e.lower_bound = 0
double_deletion_results
cysK- cysM- double knockout growth rates with cysteine-supplemented medium:
Out[65]:
b2421 b2414
b2421 1.000207 0.806868
b2414 0.806868 1.000207
 
As a example of the second category of synthetic lethal pair, disruption of modA (`b0763`) and cysA (`b2422`) results in a strain that cannot be rescued through the addition of the missing compound molybdate (`modb_e`) as the gene disruptions eliminate MOB-Dabcpp (molybdate periplasm transport through ABC system) and thus molybdate cannot be imported into the cell.
Print the reaction names associated with the two genes.

As a example of the second category of synthetic lethal pair, disruption of modA (b0763) and cysA (b2422) results in a strain that cannot be rescued through the addition of the missing compound molybdate (modb_e) as the gene disruptions eliminate MOB-Dabcpp (molybdate periplasm transport through ABC system) and thus molybdate cannot be imported into the cell.

Print the reaction names associated with the two genes.

In [66]:
 
print_gene_info(model.genes.b0763)
print_gene_info(model.genes.b2422)
cobra_id:  b0763
name:  modA
associated reactions:
MOBDabcpp ,  Molybdate transport via ABC system (periplasm)
TUNGSabcpp ,  Tungstate transport via ABC system (periplasm)
SULabcpp ,  Sulfate transport via ABC system (periplasm)

cobra_id:  b2422
name:  cysA
associated reactions:
MOBDabcpp ,  Molybdate transport via ABC system (periplasm)
SULabcpp ,  Sulfate transport via ABC system (periplasm)
TSULabcpp ,  Thiosulfate transport via ABC system (periplasm)
SLNTtpp ,  Selenite transport via proton symport (periplasm)
SELtpp ,  Selenate transport via proton symport (periplasm)

 
Compute the growth rates for the double deletion.

Compute the growth rates for the double deletion.

In [67]:
 
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b0763, model.genes.b2422}, return_frame=True)
print('modA- cysA- double knockout growth rates:')
double_deletion_results
modA- cysA- double knockout growth rates:
Out[67]:
b0763 b2422
b0763 0.982372 0.000000
b2422 0.000000 0.982372
 
Compute the growth rates for the double deletion with mobdylate-supplemented (`mobd_e`) medium. The supplementation of mobdylate in the medium cannot rescue growth in the double-deletion mutant.

Compute the growth rates for the double deletion with mobdylate-supplemented (mobd_e) medium. The supplementation of mobdylate in the medium cannot rescue growth in the double-deletion mutant.

In [68]:
 
# Supplement the medium with mobdylate
model.reactions.EX_mobd_e.lower_bound = -1000
# Compute double deletion growth rates
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b0763, model.genes.b2422}, return_frame=True)
print('modA- cysA- double knockout growth rates with mobdylate-supplemented medium:')
# Set back to the default value
model.reactions.EX_mobd_e.lower_bound = -1000
double_deletion_results
modA- cysA- double knockout growth rates with mobdylate-supplemented medium:
Out[68]:
b0763 b2422
b0763 0.982372 0.000000
b2422 0.000000 0.982372
 
#### Double gene deletion screen
Due to the relatively fast computation speed of FBA, double gene deletion analysis can be performed in a high-throughput manner. As an example, we will perform a double gene knockout screen for all genes involved in the central carbohydrates metabolism.
Because gene annotations are not available in the iJO1366 cobra model, we will retrieve the gene ontology annotations from the EcoCyc database. From the EcoCyc [web interface](http://ecocyc.org), browse the gene ontology and open the class carbohydrate metabolic process (393 instances).
<img src="Images/Ecocyc_1.png" width="500" />
Save the gene class as a SmartTable (user account log in is required). In order to list all the genes that are tagged with this gene ontology class, open the new SmartTable and add a transform column "objects annotated to GO terms". Create a new SmartTable from the objects list column (see red arrow).
<img src="Images/Ecocyc_2b.png" width="500" />
Add a new property column with the gene name corresponding to each protein.
<img src="Images/Ecocyc_3b.png" width="500" />
From the menu of the right, export the SmartTable to a spreadsheet. Choose common names for the format type, as otherwise the gene names are formatted as EcoCyc objectID by default. Move the file to the same dirctory as this notebook and rename it to "EcoCyc_carbohydrate_metabolic_process_GO.xls".
More Information:
+ EcoCyc SmartTable documentation http://biocyc.org/PToolsWebsiteHowto.shtml#node_sec_7

Double gene deletion screen

Due to the relatively fast computation speed of FBA, double gene deletion analysis can be performed in a high-throughput manner. As an example, we will perform a double gene knockout screen for all genes involved in the central carbohydrates metabolism.

Because gene annotations are not available in the iJO1366 cobra model, we will retrieve the gene ontology annotations from the EcoCyc database. From the EcoCyc web interface, browse the gene ontology and open the class carbohydrate metabolic process (393 instances). Save the gene class as a SmartTable (user account log in is required). In order to list all the genes that are tagged with this gene ontology class, open the new SmartTable and add a transform column "objects annotated to GO terms". Create a new SmartTable from the objects list column (see red arrow). Add a new property column with the gene name corresponding to each protein. From the menu of the right, export the SmartTable to a spreadsheet. Choose common names for the format type, as otherwise the gene names are formatted as EcoCyc objectID by default. Move the file to the same dirctory as this notebook and rename it to "EcoCyc_carbohydrate_metabolic_process_GO.xls".

More Information:

 
Data tables can be easily imported and handled with the [pandas package](http://pandas.pydata.org/). Pandas brings to Python data structures (dataframe) and data analysis tools similar to R.
Import the table with the `pandas.read_table` function.

Data tables can be easily imported and handled with the pandas package. Pandas brings to Python data structures (dataframe) and data analysis tools similar to R.

Import the table with the pandas.read_table function.

In [69]:
 
list_genes_GO = pandas.read_table("EcoCyc_carbohydrate_metabolic_process_GO.xls")
# Rename first column
list_genes_GO.rename(columns={list_genes_GO.columns[0]: 'reaction_name'}, inplace=True)
# Drop values with missing gene name (2 cases)
list_genes_GO = list_genes_GO.dropna()
list_genes_GO
Out[69]:
reaction_name Matches Gene
0 GLYCOGEN-BRANCH-MONOMER carbohydrate metabolic process glgB
1 1-phosphofructokinase monomer carbohydrate metabolic process fruK
2 2,3-bisphosphoglycerate-dependent phosphoglyce... carbohydrate metabolic process gpmA
3 2,3-bisphosphoglycerate-independent phosphogly... carbohydrate metabolic process gpmM
4 DEHYDDEOXGALACTKIN-MONOMER carbohydrate metabolic process dgoK
5 2-keto-3-deoxy-L-rhamnonate aldolase carbohydrate metabolic process yfaU
6 2-keto-3-deoxygluconokinase carbohydrate metabolic process kdgK
7 2-ketobutyrate formate-lyase/pyruvate formate-... carbohydrate metabolic process tdcE
8 2-methylisocitrate lyase carbohydrate metabolic process prpB
9 DEHYDDEOXPHOSGALACT-ALDOL-MONOMER carbohydrate metabolic process dgoA
10 3-deoxy-D-<i>manno</i>-octulosonate 8-phosphat... carbohydrate metabolic process kdsC
11 3-deoxy-D-<i>manno</i>-octulosonate 8-phosphat... carbohydrate metabolic process kdsA
12 3-deoxy-D-<i>manno</i>-octulosonate cytidylylt... carbohydrate metabolic process kdsB
13 3-hydroxy-2,4-pentadione 5-phosphate thiolase carbohydrate metabolic process lsrF
14 3-keto-L-gulonate 6-phosphate decarboxylase carbohydrate metabolic process sgbH
15 3-keto-L-gulonate 6-phosphate decarboxylase carbohydrate metabolic process ulaD
16 G7800-MONOMER carbohydrate metabolic process rffT
17 4-amino-4-deoxy-L-arabinose (L-Ara4N) transferase carbohydrate metabolic process arnT
18 5-keto-D-gluconate 5-reductase carbohydrate metabolic process idnO
19 6-deoxy-6-sulfofructose kinase carbohydrate metabolic process yihV
20 6-phospho-&beta;-glucosidase A carbohydrate metabolic process bglA
21 6-phospho-&beta;-glucosidase B; cryptic carbohydrate metabolic process bglB
22 6-phospho-&beta;-glucosidase; cryptic carbohydrate metabolic process ascB
23 6-phosphofructokinase-1 monomer carbohydrate metabolic process pfkA
24 6-phosphofructokinase-2 monomer carbohydrate metabolic process pfkB
25 6PGLUCONOLACT-MONOMER carbohydrate metabolic process pgl
26 AceF carbohydrate metabolic process aceF
27 AceK carbohydrate metabolic process aceK
28 aconitate hydratase 1 carbohydrate metabolic process acnA
29 ADP-heptose:LPS heptosyltransferase I carbohydrate metabolic process waaC
... ... ... ...
369 transaldolase A carbohydrate metabolic process talA
370 transaldolase B carbohydrate metabolic process talB
371 TRE6PHYDRO-MONOMER carbohydrate metabolic process treC
372 TREHALOSEPHOSPHASYN-MONOMER carbohydrate metabolic process otsB
373 TREHALOSE6PSYN-MONOMER carbohydrate metabolic process otsA
374 TreR transcriptional repressor carbohydrate metabolic process treR
375 triosephosphate isomerase monomer carbohydrate metabolic process tpiA
376 EG12666-MONOMER carbohydrate metabolic process lpxH
377 UDPACYLGLCNACDEACETYL-MONOMER carbohydrate metabolic process lpxC
378 UDP-D-galactose:(glucosyl)lipopolysaccharide-1... carbohydrate metabolic process waaB
379 UDP-D-glucose:(glucosyl)LPS &alpha;-1,3-glucos... carbohydrate metabolic process waaO
380 GALPMUT-MONOMER carbohydrate metabolic process glf
381 UDP-glucose 4-epimerase monomer carbohydrate metabolic process galE
382 UDP-glucose:(glucosyl)LPS &alpha;-1,2-glucosyl... carbohydrate metabolic process waaJ
383 G7166-MONOMER carbohydrate metabolic process arnB
384 UDP-<i>N</i>-acetyl-D-mannosamine dehydrogenase carbohydrate metabolic process wecC
385 UDPMANACATRANS-MONOMER carbohydrate metabolic process rffM
386 UDP-<i>N</i>-acetylglucosamine 2-epimerase carbohydrate metabolic process wecB
387 UGD-MONOMER carbohydrate metabolic process ugd
388 UMP phosphatase carbohydrate metabolic process umpH
389 undecaprenyl phosphate-L-Ara4FN transferase carbohydrate metabolic process arnC
390 undecaprenyl-phosphate glucose phosphotransferase carbohydrate metabolic process wcaJ
391 undecaprenyl-phosphate-&alpha;-L-Ara4N flippas... carbohydrate metabolic process arnE
392 undecaprenyl-phosphate-&alpha;-L-Ara4N flippas... carbohydrate metabolic process arnF
393 UTP--glucose-1-phosphate uridylyltransferase carbohydrate metabolic process galU
394 WzxC carbohydrate metabolic process wzxC
395 XylA carbohydrate metabolic process xylA
396 xylulokinase carbohydrate metabolic process xylB
397 YebK DNA-binding transcriptional repressor carbohydrate metabolic process yebK
398 YpdI colanic acid synthesis lipoprotein carbohydrate metabolic process ypdI

397 rows × 3 columns

 
From this list, find the matching genes in the cobra model. Iterate through the genes in the list, and for each gene, search for the gene in the cobra model with the same exact name (use `re.search` function with the case-insensitive option `re.I`). We will use the `apply` function to iterate over the rows of the dataframe.
More information:
+ [stackoverflow post](http://stackoverflow.com/questions/15118111/apply-function-to-each-row-of-pandas-dataframe-to-create-two-new-columns): Apply function to each row of pandas dataframe to create two new columns
+ Pandas documenation: [Merge, join, and concatenate](http://pandas.pydata.org/pandas-docs/stable/merging.html#ignoring-indexes-on-the-concatenation-axis)

From this list, find the matching genes in the cobra model. Iterate through the genes in the list, and for each gene, search for the gene in the cobra model with the same exact name (use re.search function with the case-insensitive option re.I). We will use the apply function to iterate over the rows of the dataframe.

More information:

In [70]:
 
# Define the function to apply at each row of the dataframe
def find_cobra_matching_gene(row):
    cobra_gene = None
    for gene in model.genes:
        if re.search(gene.name, row.Gene, re.I):
            cobra_gene = gene
    found = False if cobra_gene is None else True
    # We must return a pandas.Series in order to be able to add/merge the new columns to the original dataframe
    return pandas.Series({'cobra_gene_found':found,
                          'cobra_gene_object':cobra_gene})
# Apply the function to the rows (axis=1) of the dataframe and add the result as new columns
list_genes_GO2 = list_genes_GO.merge(list_genes_GO.apply(find_cobra_matching_gene, axis=1),
                                     left_index=True, right_index=True)
list_genes_GO2
Out[70]:
reaction_name Matches Gene cobra_gene_found cobra_gene_object
0 GLYCOGEN-BRANCH-MONOMER carbohydrate metabolic process glgB True b3432
1 1-phosphofructokinase monomer carbohydrate metabolic process fruK True b2168
2 2,3-bisphosphoglycerate-dependent phosphoglyce... carbohydrate metabolic process gpmA True b0755
3 2,3-bisphosphoglycerate-independent phosphogly... carbohydrate metabolic process gpmM True b3612
4 DEHYDDEOXGALACTKIN-MONOMER carbohydrate metabolic process dgoK True b3693
5 2-keto-3-deoxy-L-rhamnonate aldolase carbohydrate metabolic process yfaU True b2912
6 2-keto-3-deoxygluconokinase carbohydrate metabolic process kdgK True b3526
7 2-ketobutyrate formate-lyase/pyruvate formate-... carbohydrate metabolic process tdcE True b3114
8 2-methylisocitrate lyase carbohydrate metabolic process prpB True b0331
9 DEHYDDEOXPHOSGALACT-ALDOL-MONOMER carbohydrate metabolic process dgoA True b4477
10 3-deoxy-D-<i>manno</i>-octulosonate 8-phosphat... carbohydrate metabolic process kdsC True b3198
11 3-deoxy-D-<i>manno</i>-octulosonate 8-phosphat... carbohydrate metabolic process kdsA True b1215
12 3-deoxy-D-<i>manno</i>-octulosonate cytidylylt... carbohydrate metabolic process kdsB True b0918
13 3-hydroxy-2,4-pentadione 5-phosphate thiolase carbohydrate metabolic process lsrF False None
14 3-keto-L-gulonate 6-phosphate decarboxylase carbohydrate metabolic process sgbH True b3581
15 3-keto-L-gulonate 6-phosphate decarboxylase carbohydrate metabolic process ulaD True b4196
16 G7800-MONOMER carbohydrate metabolic process rffT False None
17 4-amino-4-deoxy-L-arabinose (L-Ara4N) transferase carbohydrate metabolic process arnT True b2257
18 5-keto-D-gluconate 5-reductase carbohydrate metabolic process idnO True b4266
19 6-deoxy-6-sulfofructose kinase carbohydrate metabolic process yihV False None
20 6-phospho-&beta;-glucosidase A carbohydrate metabolic process bglA True b2901
21 6-phospho-&beta;-glucosidase B; cryptic carbohydrate metabolic process bglB False None
22 6-phospho-&beta;-glucosidase; cryptic carbohydrate metabolic process ascB False None
23 6-phosphofructokinase-1 monomer carbohydrate metabolic process pfkA True b3916
24 6-phosphofructokinase-2 monomer carbohydrate metabolic process pfkB True b1723
25 6PGLUCONOLACT-MONOMER carbohydrate metabolic process pgl True b0767
26 AceF carbohydrate metabolic process aceF True b0115
27 AceK carbohydrate metabolic process aceK False None
28 aconitate hydratase 1 carbohydrate metabolic process acnA True b1276
29 ADP-heptose:LPS heptosyltransferase I carbohydrate metabolic process waaC True b3621
... ... ... ... ... ...
369 transaldolase A carbohydrate metabolic process talA True b2464
370 transaldolase B carbohydrate metabolic process talB True b0008
371 TRE6PHYDRO-MONOMER carbohydrate metabolic process treC True b4239
372 TREHALOSEPHOSPHASYN-MONOMER carbohydrate metabolic process otsB True b1897
373 TREHALOSE6PSYN-MONOMER carbohydrate metabolic process otsA True b1896
374 TreR transcriptional repressor carbohydrate metabolic process treR False None
375 triosephosphate isomerase monomer carbohydrate metabolic process tpiA True b3919
376 EG12666-MONOMER carbohydrate metabolic process lpxH True b0524
377 UDPACYLGLCNACDEACETYL-MONOMER carbohydrate metabolic process lpxC True b0096
378 UDP-D-galactose:(glucosyl)lipopolysaccharide-1... carbohydrate metabolic process waaB True b3628
379 UDP-D-glucose:(glucosyl)LPS &alpha;-1,3-glucos... carbohydrate metabolic process waaO True b3627
380 GALPMUT-MONOMER carbohydrate metabolic process glf True b2036
381 UDP-glucose 4-epimerase monomer carbohydrate metabolic process galE True b0759
382 UDP-glucose:(glucosyl)LPS &alpha;-1,2-glucosyl... carbohydrate metabolic process waaJ False None
383 G7166-MONOMER carbohydrate metabolic process arnB True b2253
384 UDP-<i>N</i>-acetyl-D-mannosamine dehydrogenase carbohydrate metabolic process wecC True b3787
385 UDPMANACATRANS-MONOMER carbohydrate metabolic process rffM False None
386 UDP-<i>N</i>-acetylglucosamine 2-epimerase carbohydrate metabolic process wecB True b3786
387 UGD-MONOMER carbohydrate metabolic process ugd True b2028
388 UMP phosphatase carbohydrate metabolic process umpH False None
389 undecaprenyl phosphate-L-Ara4FN transferase carbohydrate metabolic process arnC True b2254
390 undecaprenyl-phosphate glucose phosphotransferase carbohydrate metabolic process wcaJ False None
391 undecaprenyl-phosphate-&alpha;-L-Ara4N flippas... carbohydrate metabolic process arnE True b4544
392 undecaprenyl-phosphate-&alpha;-L-Ara4N flippas... carbohydrate metabolic process arnF True b2258
393 UTP--glucose-1-phosphate uridylyltransferase carbohydrate metabolic process galU True b1236
394 WzxC carbohydrate metabolic process wzxC False None
395 XylA carbohydrate metabolic process xylA True b3565
396 xylulokinase carbohydrate metabolic process xylB True b3564
397 YebK DNA-binding transcriptional repressor carbohydrate metabolic process yebK False None
398 YpdI colanic acid synthesis lipoprotein carbohydrate metabolic process ypdI False None

397 rows × 5 columns

 
Print out how many matching genes were found.

Print out how many matching genes were found.

In [71]:
 
print("Nb of genes in the carbohydrates metabolism category: ", len(list_genes_GO2))
print("Nb of matching genes in the cobra model: ", len(list_genes_GO2[list_genes_GO2.cobra_gene_found]))
print("Nb of genes absent in the cobra model: ", len(list_genes_GO2[~list_genes_GO2.cobra_gene_found]))
Nb of genes in the carbohydrates metabolism category:  397
Nb of matching genes in the cobra model:  253
Nb of genes absent in the cobra model:  144
 
The number of matching genes in the cobra model is lower than the number of genes from the EcoCyc database because many genes are not included in the metabolic model. Many of these genes may have unknown function.
Compute the double gene deletion growth rate for the 100 first genes in the list of cobra genes associated to the carbohydrates metabolism GO category.

The number of matching genes in the cobra model is lower than the number of genes from the EcoCyc database because many genes are not included in the metabolic model. Many of these genes may have unknown function.

Compute the double gene deletion growth rate for the 100 first genes in the list of cobra genes associated to the carbohydrates metabolism GO category.

In [72]:
 
gene_list = list(list_genes_GO2[list_genes_GO2.cobra_gene_found].cobra_gene_object)[:90]
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, gene_list, return_frame=True)
double_deletion_results
Out[72]:
b3432 b2168 b0755 b3612 b3693 b2912 b3526 b3114 b0331 b4477 ... b4232 b3371 b0825 b2800 b2802 b2801 b2255 b3128 b2094 b2093
b3432 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b2168 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b0755 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b3612 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b3693 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b2912 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b3526 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b3114 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b0331 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b4477 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 ... 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372 0.982372
b3198 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 ... 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000
b1215 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 ... 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000 0.000000
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90 rows × 90 columns

 
Plot the resulting growth rate for each of the gene pair double deletion as a 2D heat map.
Some genes are always essential, and result in a growth rate of 0 when knocked out no matter which other gene is also knocked out (horizontal and vertical blue lines). Other genes form synthetic lethal pairs, where knocking out only one of the genes has no effect on growth rate, but knocking both out is lethal (blue squares).

Plot the resulting growth rate for each of the gene pair double deletion as a 2D heat map.

Some genes are always essential, and result in a growth rate of 0 when knocked out no matter which other gene is also knocked out (horizontal and vertical blue lines). Other genes form synthetic lethal pairs, where knocking out only one of the genes has no effect on growth rate, but knocking both out is lethal (blue squares).

In [73]:
 
color_palette = seaborn.cubehelix_palette(8, start=.5, rot=-0.8, dark=0.3, light=0.9, reverse=True, as_cmap=True)
f, ax = plt.subplots(figsize=(16,14))
ax = seaborn.heatmap(double_deletion_results, cmap=color_palette, square=True, linewidths=0,
                     cbar_kws={"label":"growth rate h^-1"})
ax.tick_params(axis='both', which='major', labelsize=9)
 
From the graph, identify one new synthetic lethal pair, print out the genes information, and compute the growth rates for the corresponding double deletion.

From the graph, identify one new synthetic lethal pair, print out the genes information, and compute the growth rates for the corresponding double deletion.

In [74]:
 
print_gene_info(model.genes.b1276)
print_gene_info(model.genes.b0118)
cobra_id:  b1276
name:  acnA
associated reactions:
ACONTa ,  Aconitase (half-reaction A, Citrate hydro-lyase)
ACONTb ,  Aconitase (half-reaction B, Isocitrate hydro-lyase)

cobra_id:  b0118
name:  acnB
associated reactions:
ACONTa ,  Aconitase (half-reaction A, Citrate hydro-lyase)
MICITDr ,  2-methylisocitrate dehydratase
ACONTb ,  Aconitase (half-reaction B, Isocitrate hydro-lyase)

In [75]:
 
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b1276, model.genes.b0118}, return_frame=True)
print('acnA- acnB- double knockout growth rates:')
double_deletion_results
acnA- acnB- double knockout growth rates:
Out[75]:
b1276 b0118
b1276 0.982372 0.000000
b0118 0.000000 0.982372
 
This synthetic lethal pair was already indentified in a previous version of the E.coli metabolic model, iAF1260 (Suthers et al. 2009) and described experimentally in (Gruer et al. 1997). _acnA_ and _acnB_ genes encode for two aconitases that catalyze the reversible isomerization of citrate and iso-citrate via cis-aconitate. Deletion of both genes leads to a auxotrophic strain that can be rescued through the addition of glutamate in the medium.
<img src="Images/kim2007_metabolic_map_essential_genes.png" width="720" />
More information:
+ Suthers, P. F., Zomorrodi, A., & Maranas, C. D. (2009). Genome-scale gene/reaction essentiality and synthetic lethality analysis. Molecular Systems Biology, 5(301), 1–17. http://doi.org/10.1038/msb.2009.56
+ Gruer, M. J., Bradbury, A. J., & Guest, J. R. (1997). Construction and properties of aconitase mutants of Escherichia coli. Microbiology, 143(6), 1837–1846. http://doi.org/10.1099/00221287-143-6-1837
+ Kim, J., & Copley, S. D. (2007). Why metabolic enzymes are essential or nonessential for growth of Escherichia coli K12 on glucose. Biochemistry, 46(44), 12501–12511. http://doi.org/10.1021/bi7014629

This synthetic lethal pair was already indentified in a previous version of the E.coli metabolic model, iAF1260 (Suthers et al. 2009) and described experimentally in (Gruer et al. 1997). acnA and acnB genes encode for two aconitases that catalyze the reversible isomerization of citrate and iso-citrate via cis-aconitate. Deletion of both genes leads to a auxotrophic strain that can be rescued through the addition of glutamate in the medium.

More information:

  • Suthers, P. F., Zomorrodi, A., & Maranas, C. D. (2009). Genome-scale gene/reaction essentiality and synthetic lethality analysis. Molecular Systems Biology, 5(301), 1–17. http://doi.org/10.1038/msb.2009.56
  • Gruer, M. J., Bradbury, A. J., & Guest, J. R. (1997). Construction and properties of aconitase mutants of Escherichia coli. Microbiology, 143(6), 1837–1846. http://doi.org/10.1099/00221287-143-6-1837
  • Kim, J., & Copley, S. D. (2007). Why metabolic enzymes are essential or nonessential for growth of Escherichia coli K12 on glucose. Biochemistry, 46(44), 12501–12511. http://doi.org/10.1021/bi7014629
 
Compute the double deletion growth rates when supplementing the medium with glutamate.

Compute the double deletion growth rates when supplementing the medium with glutamate.

In [76]:
 
# Supplement the medium with glutamate
model.reactions.EX_glu__L_e.lower_bound = -1
# Compute double deletion growth rates
double_deletion_results = cobra.flux_analysis.double_gene_deletion(model, {model.genes.b1276, model.genes.b0118}, return_frame=True)
print('acnA- acnB- double knockout growth rates in glucose minimal medium supplemented with glutamate:')
# Set back to the default value
model.reactions.EX_glu__L_e.lower_bound = 0
double_deletion_results
acnA- acnB- double knockout growth rates in glucose minimal medium supplemented with glutamate:
Out[76]:
b1276 b0118
b1276 1.057030 0.930066
b0118 0.930066 1.057030